Copper-dependent cell death (cuproptosis): perspectives for pharmacological correction in human diseases

Capa


Citar

Texto integral

Acesso aberto Acesso aberto
Acesso é fechado Acesso está concedido
Acesso é fechado Acesso é pago ou somente para assinantes

Resumo

In 2022, researchers from China identified a novel form of copper-dependent cell death, termed cuproptosis, which is distinct from all previously known types of cell death. Cuproptosis is initiated by the binding of copper ions to lipoated enzymes within the Krebs cycle, leading to protein aggregation, proteotoxic stress, and, ultimately, cell death. Copper, as an essential trace element, plays a critical role in numerous physiological processes across nearly all cell types. However, intracellular copper overload can cause oxidative stress and disrupt cellular functions, necessitating tight regulation of copper homeostasis. This article provides a comprehensive summary of current knowledge on copper metabolism, copper-related diseases, and the unique characteristics and regulatory mechanisms of cuproptosis. Furthermore, it explores the role of cuproptosis in the pathogenesis of conditions such as Wilson’s disease, Menkes disease, neurodegenerative disorders, cancer, and cardiovascular diseases, alongside its potential as a therapeutic target for pharmacological intervention.

Texto integral

Acesso é fechado

Sobre autores

Vladimir Vashchenko

Kirov Military Medical Academy

Autor responsável pela correspondência
Email: vladimir-vaschenko@yandex.ru

Dr. Sci. (Biology)

Rússia, 194044 Saint Petersburg, Academician Lebedev str., 6

Alexey Chuklovin

Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation

Email: alexei.chukh@mail.ru
Código SPIN: 3050-7030

MD, Dr. Sci. (Medicine)

Rússia, Saint Petersburg

Petr Shabanov

Kirov Military Medical Academy

Email: pdshabanov@mail.ru
ORCID ID: 0000-0003-1464-1127
Código SPIN: 8974-7477

MD, Dr. Sci. (Medicine), professor

Rússia, 194044 Saint Petersburg, Academician Lebedev str., 6

Bibliografia

  1. Vashchenko VI, Vashchenko TN. Biology and pharmacology of ceruloplasmin: from experiment to drug therapy. Reviews on clinical pharmacology and drug therapy. 2009;8(1):31–44. (In Russ.)
  2. Karnaukhova IV, Shiryaeva OYu. A study of the copper content and the activity of the copper dependent superoxide dismutase in the human body. Scientific Review. Biological Science. 2018;(2):10–14. EDN: XQZFTF
  3. Lyapin AA, Tarasov RS. Modern data on methods of correction of tetrada Fallo. Cardiology and Cardiovascular Surgery. 2021;14(5):349–353.
  4. Parakhonsky AP. The role of copper in the body and the significance of its imbalance. Natural and Humanitarian Research. 2015;(10(4)):73–84. (In Russ.) EDN: VBKAYX
  5. Polenkova UI, Zubarev IV, Tomilin AN, Tsimokha AS. Ubiquitin-proteasome system in the regulation of cell pluripotency and differentiation. Tsitologiya. 2023;65(3):232–245. EDN: VDOROROR doi: 10.31857/S0041377123030069
  6. Tutelyan VA, Makhova AA, Pogozheva AV, et al. Lipoic acid: physiological role and prospects for clinical application. Problems of Nutrition. 2019;88(4):6–11. (In Russ.) EDN: OUGJJM doi: 10.24411/0042-8833-2019-10035
  7. Chukhlovin AB. Clinical significance of molecular biological diagnostics. The Scientific Notes of the Pavlov University. 2010;17(1):62–68. EDN: SMHWGT
  8. Abbas R, Larisch S. Killing by degradation: regulation of apoptosis by the ubiquitin-proteasome-system. Cells. 2021;10(12):3465. doi: 10.3390/cells10123465
  9. Adlard PA, Cherny RA, Finkelstein DI, et al. Rapid restoration of cognition in Alzheimer’s transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta. Neuron. 2008;59(1):43–55. doi: 10.1016/j.neuron.2008.06.018
  10. Aggarwal A, Bhatt M. Wilson disease. Curr Opin Neurol. 2020;33(4):534–542. doi: 10.1097/WCO.0000000000000837
  11. Aggett PJ. An overview of the metabolism of copper. Eur J Med Res. 1999;4(6):214–216.
  12. Al-Bayati MA, Jamil DA, Al-Aubaidy HA. Cardiovascular effects of copper deficiency on activity of superoxide dismutase in diabetic nephropathy. N Am J Med Sci. 2015;7(2):41–46. doi: 10.4103/1947-2714.152077
  13. Ala A, Walker AP, Ashkan K, et al. Wilson’s disease. Lancet. 2007;369(9559):397–408. doi: 10.1016/S0140-6736(07)60196-2
  14. Aliabadi F, Sohrabi B, Mostafavi E, et al. Ubiquitin-proteasome system and the role of its inhibitors in cancer therapy. Open Biol. 2021;11(4):200390. doi: 10.1098/rsob.200390
  15. Alvarez HM, Xue Y, Robinson CD, et al. Tetrathiomolybdate inhibits copper trafficking proteins through metal cluster formation. Science. 2010;327(5963):331–334. doi: 10.1126/science.1179907
  16. Al-Bayati MA, Jamil DA, Al-Aubaidy HA. Cardiovascular effects of copper deficiency on activity of superoxide dismutase in diabetic nephropathy. N Am J Med Sci. 2015;7(2):41–46. doi: 10.4103/1947-2714.152077
  17. Arciello M, Rotilio G, Rossi L. Copper-dependent toxicity in SH-SY5Y neuroblastoma cells involves mitochondrial damage. Biochem Biophys Res Commun. 2005;327(2):454–459. doi: 10.1016/j.bbrc.2004.12.022
  18. Arrasate M, Finkbeiner S. Protein aggregates in Huntington’s disease. Exp Neurol. 2012;238(1):1–11. doi: 10.1016/j.expneurol.2011.12.013
  19. Ashino T, Sudhahar V, Urao N, et al. Unexpected role of the copper transporter ATP7A in PDGF-induced vascular smooth muscle cell migration. Circ Res. 2010;107(6):787–799. doi: 10.1161/CIRCRESAHA.110.225334
  20. Atwood CS, Perry G, Zeng H, et al. Copper mediates dityrosine cross-linking of Alzheimer’s amyloid-beta. Biochemistry. 2004;43(2):560–568. doi: 10.1021/bi0358824
  21. Badet J, Soncin F, Guitton JD, et al. Specific binding of angiogenin to calf pulmonary artery endothelial cells. Proc Natl Acad Sci USA. 1989;86(21):8427–8431. doi: 10.1073/pnas.86.21.8427
  22. Baharvand M, Manifar S, Akkafan R, et al. Serum levels of ferritin, copper, and zinc in patients with oral cancer. Biomed J. 2014;37(5):331–336. doi: 10.4103/2319-4170.132888
  23. Banci L, Bertini I, Ciofi-Baffoni S, et al. Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer. Proc Natl Acad Sci USA. 2008;105(19):6803–6808. doi: 10.1073/pnas.0800019105
  24. Bandmann O, Weiss KH, Kaler SG. Wilson’s disease and other neurological copper disorders. Lancet Neurol. 2015;14(1):103–113. doi: 10.1016/S1474-4422(14)70190-5
  25. Basu S, Singh MK, Singh TB, et al. Heavy and trace metals in carcinoma of the gallbladder. World J Surg. 2013;37(11):2641–2646. doi: 10.1007/s00268-013-2164-9
  26. Behbehani GR, Barzegar L, Mohebbian M, Saboury AA. A comparative interaction between copper ions with Alzheimer’s β amyloid peptide and human serum albumin. Bioinorg Chem Appl. 2012;2012:208641. doi: 10.1155/2012/208641
  27. Berkenblit A, Eder JP Jr, Ryan DP, et al. Phase I clinical trial of STA-4783 in combination with paclitaxel in patients with refractory solid tumors. Clin Cancer Res. 2007;13(2 Pt 1):584–590. doi: 10.1158/1078-0432.CCR-06-0964
  28. Bersuker K, Hendricks JM, Li Z, et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature. 2019;575(7784):688–692. doi: 10.1038/s41586-019-1705-2
  29. Bertinato J, L’Abbé MR. Copper modulates the degradation of copper chaperone for Cu,Zn superoxide dismutase by the 26 S proteosome. J Biol Chem. 2003;278(37):35071–35078. doi: 10.1074/jbc.M302242200
  30. Bertrand E, Lewandowska E, Szpak GM, et al. Neuropathological analysis of pathological forms of astroglia in Wilson’s disease. Folia Neuropathol. 2001;39(2):73–79.
  31. Blackman RK, Cheung-Ong K, Gebbia M, et al. Mitochondrial electron transport is the cellular target of the oncology drug elesclomol. PLoS One. 2012;7(1):e29798. doi: 10.1371/journal.pone.0029798
  32. Blockhuys S, Zhang X, Wittung-Stafshede P. Single-cell tracking demonstrates copper chaperone Atox1 to be required for breast cancer cell migration. Proc Natl Acad Sci U S A. 2020;117(4):2014–2019. doi: 10.1073/pnas.1910722117
  33. Bomer N, Pavez-Giani MG, Grote Beverborg N, et al. Micronutrient deficiencies in heart failure: Mitochondrial dysfunction as a common pathophysiological mechanism? J Intern Med. 2022;291(6):713–731. doi: 10.1111/joim.13456
  34. Boyd SD, Ullrich MS, Skopp A, Winkler DD. Сopper sources for sod1 activation. Antioxidants (Basel). 2020;9(6):500. doi: 10.3390/antiox9060500
  35. Bourassa MW, Brown HH, Borchelt DR, et al. Metal-deficient aggregates and diminished copper found in cells expressing SOD1 mutations that cause ALS. Front Aging Neurosci. 2014;6:110. doi: 10.3389/fnagi.2014.00110
  36. Brady DC, Crowe MS, Turski ML, et al. Copper is required for oncogenic BRAF signalling and tumorigenesis. Nature. 2014;509(7501):492–496. doi: 10.1038/nature13180
  37. Brady DC, Crowe MS, Greenberg DN, Counter CM. Copper chelation inhibits BRAFV600E-driven melanomagenesis and counters resistance to BRAFV600E and MEK1/2 inhibitors. Cancer Res. 2017;77(22):6240–6252. doi: 10.1158/0008-5472.CAN-16-1190
  38. Brancaccio D, Gallo A, Piccioli M, et al. [4Fe-4S] Cluster assembly in mitochondria and its impairment by copper. J Am Chem Soc. 2017;139(2):719–730. doi: 10.1021/jacs.6b09567
  39. Brem S, Tsanaclis AM, Zagzag D. Anticopper treatment inhibits pseudopodial protrusion and the invasive spread of 9L gliosarcoma cells in the rat brain. Neurosurgery. 1990;26(3):391–396. doi: 10.1097/00006123-199003000-00003
  40. Brem SS, Zagzag D, Tsanaclis AM, et al. Inhibition of angiogenesis and tumor growth in the brain. Suppression of endothelial cell turnover by penicillamine and the depletion of copper, an angiogenic cofactor. Am J Pathol. 1990;137(5):1121–1142.
  41. Brewer GJ, Askari F, Lorincz MT. et al. Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a doubleblind study of treatment of the neurologic presentation of Wilson disease. Arch Neurol. 2006;63(4):521–527. doi: 10.1001/archneur.63.4.521
  42. Brewer GJ, Askari F, Dick RB, et al. Treatment of Wilson’s disease with tetrathiomolybdate: V. Control of free copper by tetrathiomolybdate and a comparison with trientine. Transl Res. 2009;154(2):70–77. doi: 10.1016/j.trsl.2009.05.002
  43. Byers PH, Siegel RC, Holbrook KA, et al. X-linked cutis laxa: defective cross-link formation in collagen due to decreased lysyl oxidase activity. N Engl J Med. 1980;303(2):61–65. doi: 10.1056/NEJM198007103030201
  44. Bucossi S, Ventriglia M, Panetta V. et al. Copper in Alzheimer’s disease: a meta-analysis of serum,plasma, and cerebrospinal fluid studies. J Alzheimers Dis. 2011;24(1):175–185. doi: 10.3233/JAD-2010-101473
  45. Bush AI. Drug development based on the metals hypothesis of Alzheimer’s disease. J Alzheimers Dis. 2008;15(2):223–240. doi: 10.3233/jad-2008-15208
  46. Cao S, Wang Q, Sun Z, et al. Role of cuproptosis in understanding diseases. Hum Cell. 2023;36(4):1244–1252. doi: 10.1007/s13577-023-00914-6
  47. Cheignon C, Tomas M, Bonnefont-Rousselot D, et al. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biol. 2018;14:450–464. doi: 10.1016/j.redox.2017.10.014
  48. Chen D, Cui QC, Yang H, et al. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res. 2006;66(21):10425–10433. doi: 10.1158/0008-5472.CAN-06-2126
  49. Chen J, Li X, Ge C., et al. The multifaceted role of ferroptosis in liver disease. Cell Death Differ. 2022;29(3):467–480. doi: 10.1038/s41418-022-00941-0
  50. Chen QY, Wu P, Wen T, et al. Association of cerebral spinal fluid copper imbalance in amyotrophic lateral sclerosis. Front Aging Neurosci. 2022;14:970711. doi: 10.3389/fnagi.2022.970711.
  51. Chen X, Cai Q, Liang R, et al. Сopper homeostasis and copper induced cell phatogenesis of cardiovascular disease and therapeutic strategies. Cell Death Dis. 2023;14(2):105. doi: 10.1038 / s41419-023-05639-w
  52. Cherny RA, Atwood CS, Xilinas ME, et al. Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer’s disease transgenic mice. Neuron. 2001;30(3):665–676. doi: 10.1016/s0896-6273(01)00317-8
  53. Cherny RA, Ayton S, Finkelstein DI, et al. PBT2 reduces toxicity in a C. elegans model of polyQ aggregation and extends lifespan, reduces striatal atrophy and improves motor performance in the R6/2 mouse model of huntington’s disease. J Huntingtons Dis. 2012;1(2):211–219. doi: 10.3233/JHD-120029
  54. Christgen S, Tweedell RE, Kanneganti TD. Programming inflammatory cell death for therapy. Pharmacol Ther. 2022;232:108010. doi: 10.1016/j.pharmthera.2021.108010
  55. Ciavarella S, Milano A, Dammacco F, Silvestris F. Targeted therapies in cancer. BioDrugs. 2010:24(2):77–88. doi: 10.2165/11530830-000000000-00000 2010
  56. Cobine PA, Pierrel F, Winge DR. Copper trafficking to the mitochondrion and assembly of copper metalloenzymes. Biochim Biophys Acta. 2006;1763(7):759–772. doi: 10.1016/j.bbamcr.2006.03.002
  57. Cox C, Teknos TN, Barrios M, et al. The role of copper suppression as an antiangiogenic strategy in head and neck squamous cell carcinoma. Laryngoscope. 2001;111(4 Part 1):696–701. doi: 10.1097/00005537-200104000-00024
  58. Cox TR, Rumney RMH, Schoof EM, et al. The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature. 2015;522(7554):106–110. doi: 10.1038/nature14492
  59. Crouch PJ, Savva MS, Hung LW, et al. The Alzheimer’s therapeutic PBT2 promotes amyloid-beta degradation and GSK3 phosphorylation via a metal chaperone activity. J Neurochem. 2011;119(1):220–230. doi: 10.1111/j.1471-4159.2011.07402.x
  60. Crowe A, Jackaman C, Beddoes KM, et al. Rapid copper acquisition by developing murine mesothelioma: decreasing bioavailable copper slows tumor growth, normalizes vessels and promotes T cell infiltration. PLoS ONE. 2013;8(8):e73684. doi: 10.1371/journal.pone.0073684
  61. Czlonkowska A, Litwin T, Dusek P, et al. Wilson disease. Nat Rev Dis Prim. 2018;4(1):21. doi: 10.1038/s41572-018-0018-3
  62. Dancis А, Roman DG, Аnderson GJ, et al. Ferric reductase of Saccharomyces cerevisiae: molecular characterization, role in iron uptake, and transcriptional control by iron. Proc Natl Acad Sci USA. 1992;89(9):3869–3873. doi: 10.1073 /pnas.89.9.3869
  63. Deng L, Meng T, Chen L, et al. The role of ubiquitination in tumorigenesis and targeted drug discovery. Signal Transduct Target Ther. 2020;5(1):11. doi: 10.1038/s41392-020-0107-0
  64. Denoyer D, Masaldan S, La Fontaine S, Cater MA. Targeting copper in cancer therapy: ’Copper That Cancer’. Metallomics. 2015;7(11):1459–1476. doi: 10.1039 /c5mt00149h
  65. Denoyer D, Pearson HB, Clatworthy SAS, et al. Copper as a target for prostate cancer therapeutics: copperionophore pharmacology and altering systemic copper distribution. Oncotarget. 2016;7(24):37064–37080. doi: 10.18632/oncotarget.9245
  66. Dexter DT, Carayon A, Jaroy-Agid F, et al. Alterations in the levels of iron, ferritin and other trace metals in Parkinson’s disease and other neurodegenerative diseases affecting the basal ganglia. Brain. 1991;114(Part 4):1953–1975. doi: 10.1093/brain/114.4.1953
  67. Diez M, Arroyo M, Cerdan FJ, et al. Serum and tissue trace metal levels in lung cancer. Oncology. 1989;46(4):230–234. doi: 10.1159/000226722
  68. DiFiglia M, Sapp E, Chase KO, et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science. 1997;277(5334):1990–1993. doi: 10.1126/science.277.5334.1990
  69. DiNicolantonio JJ, Mangan D, O’Keefe JH. Copper deficiency may be a leading cause of ischaemic heart disease. Open Heart. 2018;5(2):e000784. doi: 10.1136/openhrt-2018-000784
  70. Doll S, Freitas S, Shah R, et al. FSP1 is a glutathione-independent ferroptosis suppressor. Nature. 2019;575():693–698. doi: 10.1038/s41586-019-1707-0
  71. Donate F, Juarez JC, Burnett ME, et al. Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224). Br J Cancer. 2008;98(4):776–783. doi: 10.1038/sj.bjc.6604226
  72. Du X, Zhang Y, Wang Z, et al. Inhibitory act of selenoprotein P on Cu(+)/Cu(2+)-induced tau aggregation and neurotoxicity. Inorg Chem. 2014;53(20):11221–11230. doi: 10.1021/ic501788v
  73. Dusek P., Litwin T, Czlonkowska A. Wilson disease and other neurodegenerations with metal accumulations. Neurol Clin. 2015;33(1):175–204. doi: 10.1016/j.ncl.2014.09.006
  74. Elchuri S, Oberley TD, Qi W, et al. CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene. 2005;24(3):367–380. doi: 10.1038/sj.onc.1208207
  75. Elsherif L, Wang L, Saari JT, Kang YJ. Regression of dietary copper restriction-induced cardiomyopathy by copper repletion in mice. J Nutr. 2004;134(4): 855–860. doi: 10.1093/jn/134.4.855
  76. Elsasser S, Finley D. Delivery of ubiquitinated substrates to protein-unfolding machines. Nat. Cell Biol. 2005;7(8):742–749. doi: 10.1038/ncb0805-742
  77. Enge TG, Ecroyd H, Jolley DF, et al. Longitudinal assessment of metal concentrations and copper isotope ratios in the G93A SOD1 mouse model of amyotrophic lateral sclerosis. Metallomics. 2017;9(2):161–174. doi: 10.1039/c6mt00270f
  78. Erler JT, Bennewith KL, Cox TR, et al. Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell. 2009;15(1):35–44. doi: 10.1016/j.ccr.2008.11.012
  79. Eskici G, Axelsen PH. Copper and oxidative stress in the pathogenesis of Alzheimer’s disease. Biochemistry. 2012;51(32):6289–6311. doi: 10.1021/bi3006169
  80. Factor SM, Cho S, Sternlieb I, et al. The cardiomyopathy of Wilson’s disease. Myocardial alterations in nine cases. Virchows Arch A Pathol Anat Histol. 1982;397(3):301–311. doi: 10.1007/BF00496571
  81. Fang X, Cai Z, Wang H, et al. Loss of cardiac ferritin H facilitates cardiomyopathy via Slc7a11-mediated ferroptosis. Circ Res. 2020;127(4):486–501. doi: 10.1161/CIRCRESAHA.120.316509
  82. Fang X, Ardehali H, Min J, Wang F. The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease. Nat Rev Cardiol. 2022;1:7–23. doi: 10.1038/s41569-022-00735-4
  83. Fang X, Wang H, Han D, et al. Ferroptosis as a target for protection against cardiomyopathy. Proc Natl Acad Sci USA. 2019;116(7):2672–2680. doi: 10.1073/pnas.1821022116
  84. Faux NG, Ritchie CW, Gunn A, et al. PBT2 rapidly improves cognition in Alzheimer’s disease: additional phase II analyses. J Alzheimers Dis. 2010;20(2):509–516. doi: 10.3233/JAD-2010-1390
  85. Feng W, Ye F, Xue W, et al. Copper regulation of hypoxiainducible factor-1 activity. Mol Pharmacol. 2009;75(1):174–182. doi: 10.1124/mol.108.051516
  86. Feng JF, Lu L, Zeng P, et al. Serum total oxidant/antioxidant status and trace element levels in breast cancer patients. Int J Clin Oncol. 2012;17(6):575–583. doi: 10.1007/s10147-011-0327-y
  87. Festa RA, Thiele DJ. Copper: an essential metal in biology. Curr Biol. 2011;21(21):R877–R883. doi: 10.1016/j.cub.2011.09.040
  88. Ford ES. Serum copper concentration and coronary heart disease among US adults. Am J Epidemiol. 2000;151(12):1182–1188. doi: 10.1093/oxfordjournals.aje.a010168
  89. Fox JH, Kama JA, Lieberman G., et al. Mechanisms of copper ion mediated Huntington’s disease progression. PLoS ONE. 2007;2(3):e334. doi: 10.1371/journal.pone.0000334
  90. Freisinger P, Horvath R, Macmillan C, et al. Reversion of hypertrophic cardiomyopathy in a patient with deficiency of the mitochondrial copper binding protein Sco2: is there a potential effect of copper? J Inherit Metab Dis. 2004;27(1):67–79. doi: 10.1023/B:BOLI.0000016614.47380.2f
  91. Galluzzi L, Vitale I, Aaronson SA. et al. Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. Cell Death Different. 2018;25(3):486–541. doi: 10.1016/j.jtho.2016.05.021
  92. Gao F, Yuan Y, Ding Y, et al. DLAT as a cuproptosis promoter and a molecular target of elesclomol in hepatocellular carcinoma. Curr Med Sci. 2023;43(3):526–538. doi: 10.1007/s11596-023-2755-0
  93. Garcia-Santamarina S, Uzarska MA, Festa RA, et al. Cryptococcus neoformans iron–sulfur proteinbiogenesis machinery is a novel layer of protection against Cu stress. mBio. 2017;8(5):e01742–17. doi: 10.1128/mBio.01742-17
  94. Georgatsou E, Mavrogiannis LA, Fragiadakis GS, Alexandraki D. The yeast Fre1p/Fre2p cupric reductases facilitate copper uptake and are regulated by the copper-modulated Mac1p activator. J Biol Chem. 1997;272(21):13786–13792. doi: 10.1074/jbc.272.21.13786
  95. George DH, Casey RE. Menkes disease after copper histidine replacement therapy: case report. Pediatr Dev Pathol. 2001;4(3):281–288. doi: 10.1007/s100240010142
  96. Gralla EB, Valentine JS. Null mutants of Saccharomyces cerevisiae Cu,Zn superoxide dismutase: characterization and spontaneous mutation rates. J Bacteriol. 1991;173(18):5918–5920. doi: 10.1128/jb.173.18.5918-5920.1991
  97. Gromadzka G, Tarnacka B, Flaga A, Adamczyk A. Copper dyshomeostasis in neurodegenerative diseases Therapeutic Implications. Int J Mol Sci. 2020;21(23):9259. doi: 10.3390/ijms21239259
  98. Gu M, Cooper JM, Butler P, et al. Oxidative-phosphorylation defects in liver of patients with Wilson’s disease. Lancet. 2000;356(9228):469–474. doi: 10.1016/s0140-6736(00)02556-3
  99. Gupta SK, Shukla VK, Vaidya MP, et al. Serum and tissue trace elements in colorectal cancer. J Surg Oncol. 1993;52(3):172–175. doi: 10.1002/jso.2930520311
  100. Gupte A, Mumper RJ. Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. Cancer Treat Rev. 2009;35(1):32–46. doi: 10.1016/j.ctrv.2008.07.004
  101. Guzior N, Wieckowska A, Panek D, Malawska B. Recent development of multifunctional agents as potential drug candidates for the treatment of Alzheimer’s disease. Curr Med Chem. 2015;22(3):373–404. doi: 10.2174/0929867321666141106122628
  102. Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem. 2006;97(6):1634–1658. doi: 10.1111/j.1471-4159.2006.03907.x
  103. Hamza I, Prohaska J, Gitlin JD. Essential role for Atox1 in the coppermediated intracellular trafficking of the Menkes ATPase. Proc Natl Acad Sci USA. 2003;100(3):1215–1220. doi: 10.1073/pnas.0336230100
  104. Hands SL, Mason R, Sajjad MU, et al. Metallothioneins and copper metabolism are candidate therapeutic targets in Huntington’s disease. Biochem Soc Trans. 2010;38(2):552–558. doi: 10.1042/BST0380552
  105. Harms L, Meierkord H, Timm G, et al. Decreased nacetyl-aspartate/choline ratio and increased lactate in the frontal lobe of patients with Huntington’s disease: a proton magnetic resonance spectroscopy study. J Neurol Neurosurg Psychiatry. 1997;62(1):27–30. doi: 10.1136/jnnp.62.1.27
  106. Heaton DN, George GN, Garrison G, Winge DR. The mitochondrial copper metallochaperone Cox17 exists as an oligomeric, polycopper complex. Biochemistry. 2001;40(3):743–751. doi: 10.1021/bi002315x
  107. Hicks JD, Domsante A, Pierson TM, et al. Increased frequency of congenital heart defects in Menkes disease. Clin Dysmorphol. 2012;21(2):59–63. doi: 10.1097/MCD.0b013e32834ea52b
  108. Hilton JB, Merser SU, Lim NKH, et al. Cu(II)(atsm) improves the neurological phenotype and survival of SOD1(G93A) mice and selectively increases enzymatically active SOD1 in the spinal cord. Sci Rep. 2017;7:42292. doi: 10.1038/srep42292
  109. Hottinger AF, Fine EG, Gurney ME, et al. The copper chelator D-penicillamine delays onset of disease and extends survival in a transgenic mouse model of familial amyotrophic lateral sclerosis. Eur J Neurosci. 1997;9(7):1548–1551. doi: 10.1111/j.1460-9568.1997.tb01511.x
  110. Horng YC, Cobine PA, Maxfield AB, et al. Specificcopper transfer from the Cox17 metallochaperone to both Sco1 and Cox11 in the assembly of yeast cytochrome C oxidase. J Biol Chem. 2004;279(34):35334–35340. doi: 10.1074/jbc.M404747200
  111. Huang J, Campian JL, Gujar AD, et al. A phase I study to repurpose disulfiram in combination with temozolomide to treat newly diagnosed glioblastoma after chemoradiotherapy. J Neurooncol. 2016;128(2):259–266. doi: 10.1007/s11060-016-2104-2
  112. Huster D. Structural and metabolic changes in Atp7b-/- mouse liver and potential for new interventions in Wilson’s disease. Ann NY Acad Sci. 2014;1315:37–44. doi: 10.1111/nyas.12337
  113. Jakola AS, Werlenius K, Mudaisi M, et al. Disulfiram repurposing combined with nutritional copper supplement as add-on to chemotherapy in recurrent glioblastoma (DIRECT): Study protocol for a randomized controlled trial. F1000Res. 2018;7:1797. doi: 10.12688/f1000research.16786.1
  114. Jaksch M, Ogilvie I, Yao J, et al. Mutations in SCO2 are associated with a distinct form of hypertrophic cardiomyopathy and cytochrome c oxidase deficiency. Hum Mol Genet. 2000;9(5):795–801. doi: 10.1093/hmg/9.5.795
  115. James SA, Churces QI, de Jonge MD, et al. Iron, copper, and zinc concentration in A beta plaques in the APP/PS1 mouse model of Alzheimer’s disease correlates with metal levels in the surrounding neuropil. ACS Chem Neurosci. 2017;8(3):629–637. doi: 10.1021/acschemneuro.6b00362
  116. Jenagaratnam L, McShane R. Clioquinol for the treatment of Alzheimer’s disease. Cochrane Database Syst Rev. 2006;25(1):CD005380. doi: 10.1002/14651858.CD005380.pub2
  117. Ji MB, Arbel M, Zhang L, et al. Label-free imaging of amyloid plaques in Alzheimer’s disease with stimulated Raman scattering microscopy. Sci Adv. 2018;4(11):eaat7715. doi: 10.1126/sciadv.aat7715
  118. Jiang Y, Huo Z, Qi X, et al. Copper-induced tumor cell death mechanisms and antitumor theragnostic applications of copper complexes. Nanomedicine (Lond). 2022;17(5):303–324. doi: 10.2217/nnm-2021-0374
  119. Ishida S, Andreux P, Poitry-Yamate C, et al. Bioavailable copper modulates oxidative phosphorylation and growth of tumors. Proc Natl Acad Sci USA. 2013;110(48):19507–19512. doi: 10.1073/pnas.1318431110
  120. Itoh S, Kim HW, Nakagawa O, et al. Novel role of antioxidant-1 (Atox1) as a copper-dependent transcription factor involved in cell proliferation. J Biol Chem. 2008;283(14):9157–9167. doi: 10.1074/jbc.M709463200
  121. Kaler SG, Gahl WA, Berry SA, et al. Predictive value of plasma catecholamine levels in neonatal detection of Menkes disease. J Inherit Metab Dis. 1993;16(5):907–908. doi: 10.1007/BF00714295
  122. Kaler SG, Holmes CS, Goldstein DS, et al. Neonatal diagnosis and treatment of Menkes disease. N Engl J Med. 2008;358(6):605–614. doi: 10.1056/NEJMoa070613
  123. Kaler SG. Neurodevelopment and brain growth in classic Menkes disease is influenced by age and symptomatology at initiation of copper treatment. J Trace Elem Med Biol. 2014;28(4):427–430. doi: 10.1016/j.jtemb.2014.08.008
  124. Kang YJ, Wu H, Saari JT. Alterations in hypertrophic gene expression by dietary copper restriction in mouse heart. Proc Soc Exp Biol Med. 2000;223:282–287. doi: 10.1046/j.1525-1373.2000.22340.x
  125. Kang X, Jadhav S, Annaji M, et al. Advancing cancer therapy with copper/disulfiram nanomedicines and drug delivery systems. Pharmaceutics. 2023;15(6):1567. doi: 10.3390/pharmaceutics15061567
  126. Kasischke KA, Vishwasrao HD, Fisher PJ, et al. Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science. 2004;305(5680):99–103. doi: 10.1126/ science.1096485
  127. Ke D, Zhang Z, Liu J, et al. Ferroptosis, necroptosis and cuproptosis: Novel forms of regulated cell death in diabetic cardiomyopathy. Front Cardiovasc Med. 2023;10:1135723. doi: 10.3389/fcvm.2023.1135723
  128. Kim BE, Turski ML, Nose Y, et al. Cardiac copper deficiency activates a systemic signaling mechanism that communicates with the copper acquisition and storage organs. Cell Metab. 2010;11(5):353–363. doi: 10.1016/j.cmet.2010.04.003
  129. Kim JH, Lee BH, Kim YM, et al. Novel mutations and clinical outcomes of copper-histidine therapy in Menkes disease patients. Metab Brain Dis. 2015;30(1):75–81. doi: 10.1007/s11011-014-9569-5
  130. Kim KK, Abelman S, Yano N, et al. Tetrathiomolybdate inhibits mitochondrial complex IV and mediates degradation of hypoxia-inducible factor-1alpha in cancer cells. Sci Rep. 2015;5:14296. doi: 10.1038/srep14296
  131. Kirshner JR, He S, Balasubramanyam V, et al. Elesclomol induces cancer cell apoptosis through oxidative stress. Mol Cancer Ther. 2008;7(8):2319–2327. doi: 10.1158/1535-7163.MCT-08-0298
  132. Kitazawa M, Hsu HW, Medeiros R. Copper exposure perturbs brain inflammatory responses and impairs clearance of amyloid-beta. Toxicol Sci. 2016;152(1):194–204. doi: 10.1093/toxsci/kfw081
  133. Kohno T, Urao N, Ashino T, et al. Novel role of copper transport protein antioxidant-1 in neointimal formation after vascular injury. Arterioscler Thromb Vasc Biol. 2013;33(4):805–813. doi: 10.1161/ATVBAHA.112.300862
  134. Kok FJ, Van Duijn CM, Hofman A, et al. Serum copper and zinc and the risk of death from cancer and cardiovascular disease. A J Epidem. 1988;128(2):352–359. doi: 10.1093/oxfordjournals.aje.a114975
  135. Kong R, Sun G. Targeting copper metabolism: a promising strategy for cancer treatment. Front Pharmacol. 2023;14:1203447. doi: 10.3389/fphar.2023.1203447
  136. Kopeina GS, Zhivotovsky B. Programmed cell death: Past, present and future. Biochem Biophys Res Commun. 2022;633:55–58. doi: 10.1016/j.bbrc.2022.09.022
  137. Kumari N, Choi SH. Tumor-associated macrophages in cancer: recent advancements in cancer nanoimmunotherapies. J Exp Clin Cancer Res. 2022;41(1):68. doi: 10.1186/s13046-022-02272-x
  138. Kuo YM, Gybina AA, Pyatskowit JW, et al. Copper transport protein (Ctr1) levels in mice are tissue specific and dependent on copper status. J Nutr. 2006;136(1):21–26. doi: 10.1093/jn/136.1.21
  139. La Fontaine S, Ackland ML, Mercer JF. Mammalian copper-transporting Ptype ATPases, ATP7A and ATP7B: emerging roles. Int J Biochem Cell Biol. 2010;42(2):206–209. doi: 10.1016/j.biocel.2009.11.007
  140. La Fontaine S, Mercer JF. Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis. Arch Biochem Biophys. 2007;463(2):149–167. doi: 10.1016/j.abb.2007.04.021
  141. Lang M, Fan Q, Wang L, Inhibition of human high-affinity copper importer Ctr1 orthologous in the nervous system of Drosophila ameliorates Abeta42-induced Alzheimer’s disease-like symptoms. Neurobiol Aging. 2013;34(11):2604–2612. doi: 10.1016/j.neurobiolaging.2013.05.029
  142. Lannfelt L, Blennow K, Zetterberg H, et al. Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer’s disease: a phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2008;7(9):779–786. doi: 10.1016/S1474-4422(08)70167-4
  143. Leary SC, Kaufman BA, Pellecchia G, et al. Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase. Hum Mol Genet. 2004;13(17):1839–1848. doi: 10.1093/hmg/ddh197
  144. Lee J, Petris MJ, Thiele DJ. Characterization of mouse embryonic cells deficient in the ctr1 high affinity copper transporter. Identification of a Ctr1-independent copper transport system. J Biol Chem. 2002;277(43):40253–40259. doi: 10.1074/jbc.M208002200
  145. Lei P, Ayton S, Bush AI. The essential elements of Alzheimer’s disease. J Biol Chem. 2021;296:100105. doi: 10.1074/jbc.REV120.008207
  146. Lelie HL, Liba A, Bourassa MW, et al. Copper and zinc metallation status of copper-zinc superoxide dismutase from amyotrophic lateral sclerosis transgenic mice. J Biol Chem. 2011;286(4):2795–2806. doi: 10.1074/jbc.M110.186999
  147. Lener MR, Scott RJ, Wiechowska-Kozlowska A, et al. Serum concentrations of selenium and copper in patients diagnosed with pancreatic cancer. Cancer Res Treat. 2016;48(3):1056–1064. doi: 10.4143/crt.2015.282
  148. Li DD, Zhang W, Wang ZY, Zhao P. Serum copper, zinc, and iron levels in patients with Alzheimeras disease: a meta-analysis of case-control studies. Front Aging Neurosci. 2017;9:300. doi: 10.3389/fnagi.2017.00300
  149. Liang ZD, Tsai WD, Lee MY, et al. Specificity protein 1 (sp1) oscillation is involved in copper homeostasis maintenance by regulating human high-affinity copper transporter 1 expression. Mol Pharmacol. 2020;8(1):155–464. doi: 10.1124/mol.111.076422
  150. Linz R, Lutsenko S. Copper-transporting ATPases ATP7A and ATP7B: cousins, not twins. J Bioenerg Biomembr. 2007;39(5-6):403–407. doi: 10.1007/s10863-007-9101-2
  151. Liu N, Lo LS, Askary SH, et al. Transcuprein is a macroglobulin regulated by copper and iron availability. J Nutr Biochem. 2007;18(9):597–608. doi: 10.1016/j.jnutbio.2006.11.005
  152. Liu P, Brown S, Goktug T, et al. Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells. Br J Cancer. 2012;107(9):1488–1497. doi: 10.1038/bjc.2012.442
  153. Liu P, Kumar JS, Brown S, et al. Disulfiram targets cancer stem-like cells and reverses resistance and cross-resistance in acquired paclitaxel-resistant triple-negative breast cancer cells. Br J Cancer. 2013;109(7):1876–1885. doi: 10.1038/bjc.2013.534
  154. Lonial S, Mitsiades CS, Richardson PG. Treatment options for relapsed and refractory multiple myeloma. Clin Cancer Res. 2011;17(6):1264–1277. doi: 10.1158/1078-0432.CCR-10-1805
  155. Lun X, Wells C, Grinshteiin N, et al. Disulfiram when combined with copper enhances the therapeutic effects of temozolomide for the treatment of glioblastoma. Clin Cancer Res. 2016;22(15):3860–3875. doi: 10.1158/1078-0432.CCR-15-1798
  156. Luoqian J, Yang W, Ding X, et al. Ferroptosis promotes T-cell activation-induced neurodegeneration in multiple sclerosis. Cell Mol Immunol. 2022;19(8):913–924. doi: 10.1038 / s41423-022-00883-0
  157. Lutsenko S, Barnes NL, Bartee MY, Dmitriev OY. Function and regulation of human copper-transporting ATPases. Physiol Rev. 2007;87(3):1011–1046. doi: 10.1152/physrev.00004.2006
  158. Lutsenko S, Bhattacharjee A, Hubbard AL. Copper handling machinery of the brain. Metallomics. 2010;2(9):596–608. doi: 10.1039/c0mt00006j
  159. Lutsenko S. Copper trafficking to the secretory pathway. Metallomics. 2016;8(9):840–852. doi: 10.1039/c6mt00176a
  160. Lucena-Valera A, Ruz-Zafra P, Ampuero J. Wilson disease: overview. Med Clin (Barc). 2023;160(6):261–267. doi: 10.1016/j.medcli.2022.12.016
  161. Lynch SM, Colon W. Dominant role of copper in the kinetic stability of Cu/Zn superoxide dismutase. Biochem Biophys Res Commun. 2006;340(2):457–461. doi: 10.1016/j.bbrc.2005.12.024
  162. Mammoto T, Jiang A, Jiang E, et al. Role of collagen matrix in tumor angiogenesis and glioblastoma multiforme progression. Am J Pathol. 2013;183(4):1293–1305. doi: 10.1016/j.ajpath.2013.06.026
  163. Michniewicz F, Saletta F, Rouaen JRC, et al. Copper: An intracellular achilles’ heel allowing the targeting of epigenetics, kinase pathways, and cell metabolism in cancer therapeutics. Chem Med Chem. 2021;16(15):2315–29. doi: 10.1002/cmdc.202100172
  164. Maffia M, Greco M, Rizzo F, et al. Copper dyshomeostasis in neurodegenerative diseases. Acta Physiologica. 2019;227:58–58.
  165. Mayr JA, Feichtinger RG, Tort F, et al. Lipoic acid biosynthesis defects. J Inherit Metab Dis. 2014;37(4):553–563. doi: 10.1007/s10545-014-9705-8
  166. Margalioth EJ, Schenker JG, Chevion M. Copper and zinc levels in normal and malignant tissues. Cancer. 1983;52(5):868–872. doi: 10.1002/1097-0142(19830901)52:5<868::aid-cncr2820520521>3.0.co;2-k
  167. Maung MT, Carlson A, Olea-Flores M, et al. The molecular and cellular basis of copper dysregulation and its relationship with human pathologies. FASEB J. 2021;35(9)e21810. doi: 10.1096/fj.202100273RR
  168. McAuslan BR, Reilly W. Endothelial cell phagokinesis in response to specific metal ions. Exp Cell Res. 1980;130(1):147–157. doi: 10.1016/0014-4827(80)90051-8
  169. Medeiros DM, Wildman RE. Newer findings on a unified perspective of copper restriction and cardiomyopathy. Proc Soc Exp Biol Med. 1997;215(4):299–313. doi: 10.3181/00379727-215-44141
  170. Misra AK, Biswas A, Ganguly G, et al. Arthropathic presentation of Wilson’s disease. J Assoc Physicians India. 2004;52:246–248.
  171. Moller LB, Mogensen M, Horn N. Molecular diagnosis of Menkes disease: genotype–phenotype correlation. Biochimie. 2009;91(10):1273–1277. doi: 10.1016/j.biochi.2009.05.011
  172. Moriguchi M, Nakajima T, Kimura H, et al. The copper chelator trientine has an antiangiogenic effect against hepatocellular carcinoma, possibly through inhibition of interleukin-8 production. Int J Cancer. 2002;102(5):445–452. doi: 10.1002/ijc.10740
  173. Moriya M, Ho Yi-H, Grana A, et al. Copper is taken up efficiently from albumin and alpha2-macroglobulin by cultured human cells by more than one mechanism. Am J Physiol Cell Physiol. 2008;295(3):C708–C721. doi: 10.1152/ajpcell.00029.2008
  174. Nagai M, Vo NH, Ogawa LS, et al. The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells. Free Radic Biol Med. 2012;52(10): 2142–2150. doi: 10.1016/j.freeradbiomed.2012.03.017
  175. Nandi D, Tahiliani P, Kumar A, Chandu D. The ubiquitin-proteasome system. J Biosci. 2006;31(1):137–155. doi: 10.1007/BF02705243
  176. Nayak SB, Bhat VR, Upadhyay D, Udupa SL. Copper and ceruloplasmin status in serum of prostate and colon cancer patients. Indian J Physiol Pharmacol. 2003;47(1):108–110.
  177. Nikseresht S, Hilton JBW, Kysenius K, et al. Copper-atsm as a treatment for ALS: support from mutant sod1 models and beyond. Life (Basel). 2020;10(11):271. doi: 10.3390/life10110271
  178. Noda Y, Asada M, Kubota M, et al. Copper enhances APP dimerization and promotes Abeta production. Neurosci Lett. 2013;547:10–15. doi: 10.1016/j.neulet.2013.04.057
  179. Nose Y, Kim BE, Thiele DJ. Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function. Cell Metab. 2006;4(3):235–244. doi: 10.1016/j.cmet.2006.08.009
  180. Nyvltova E, Dietz JV, Seravalli J, et al. Coordination of metal center biogenesis in human cytochrome c oxidase. Nat Commun. 2022;13(1):3615. doi: 10.1038/s41467-022-31413-1
  181. O’Day SJ, Eggermont AMM, Chiarion-Sileni V, et al. Final results of phase III symmetry study: randomized, doubleblind trial of elesclomol plus paclitaxel versus paclitaxel alone as treatment for chemotherapy-naive patients with advanced melanoma. J Clin Oncol. 2013;31(9):1211–1218. doi: 10.1200/JCO.2012.44.5585
  182. Ojha R, Prasad AN. Menkes disease: what a multidisciplinary approach can do. J Multidiscip Healthc. 2016;9:371–385. doi: 10.2147/JMDH.S93454
  183. Ohgami RS, Campagna DR, McDonald A, Fleming MD. The Steap proteins are metalloreductases. Blood. 2006;108(4):1388–1394. doi: 10.1182/blood-2006-02-003681
  184. Okado-Matsumoto A, Fridovich I. Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu, Zn-SOD in mitochondria. J Biol Chem. 2001;276(42):38388–38393. doi: 10.1074/jbc.M105395200
  185. Osawa T, Ohga N, Akiyama K, et al. Lysyl oxidase secreted by tumour endothelial cells promotes angiogenesis and metastasis. Br J Cancer. 2013;109(8):2237–2247. doi: 10.1038/bjc.2013.535
  186. Palmgren MG, Nissen P. P-type ATPases. Annu Rev Biophys. 2011;40:243–266. doi: 10.1146/annurev.biophys.093008.131331
  187. Pan Q, Bao LW, Merajver SD. Tetrathiomolybdate inhibits angiogenesis and metastasis through suppression of the NFkappaB signaling cascade. Mol Cancer Res. 2003;1(10):701–706.
  188. Pan Q, Rosenthal DT, Bao L. et al. Antiangiogenic tetrathiomolybdate protects against Her2/neu-induced breast carcinoma by hypoplastic remodeling of the mammary gland. Clin Cancer Res. 2009;15(23):7441–7446. doi: 10.1158/1078-0432.CCR-09-1361
  189. Pan Q, Kleer CG, van Golen KL, et al. Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and angiogenesis. Cancer Res. 2002;62(17):4854–4859.
  190. Pamp K, Bramey T, Kirsch M, et al. NAD(H) enhances the Cu(II)-mediated inactivation of lactate dehydrogenase by increasing the accessibility of sulfhydryl groups. Free Radic Res. 2005;39(1):31–40. doi: 10.1080/10715760400023671
  191. Park W, Wei S, Kim BS, et al. Diversity and complexity of cell death: a historical review. Exper Mol Med. 2023;55(8):1573–1594. doi: 10.1038/s12276-023-01078-x
  192. Patterson BD, Foley PF, Ueno H, et al. Class II malocclusion correction with Invisalign: Is it possible? Am J Orthod Dentofacial Orthop. 2021;159(1):e41–e48. doi: 10.1016/j.ajodo.2020.08.016
  193. Pavithra V, Sathisha TG, Kasturi K, et al. Serum levels of metal ions in female patients with breast cancer. J Clin Diagn Res. 2015;9(1):BC25–c27. doi: 10.7860/JCDR/2015/11627.5476
  194. Peng J, Wang P, Chen H, et al. Potential of copper and copper compounds for anticancer applications. Pharmaceutical (Basel). 2023;16(2):234. doi: 10.3390/ph16020234
  195. Poujois A, Woimant F. Wilson’s disease: a 2017 update. Clin Res Hepatol Gastroenterol. 2018;42(6):512–520. doi: 10.1016/j.clinre.2018.03.007
  196. Pratt AJ, Sin D, Merts GE, et al. Aggregation propensities of superoxide dismutase G93 hotspot mutants mirror ALS clinical phenotypes. Proc Natl Acad Sci. USA. 2014;111(43): E4568–E4576. doi: 10.1073/pnas.1308531111
  197. Prohaska JR., Geissler J, Brokate B, Broderius M. Copper, zinc-superoxide dismutase protein but not mRNA is lower in copper-deficient mice and mice lacking the copper chaperone for superoxide dismutase. Exp Biol Med. (Maywood). 2003;228(8):959–966. doi: 10.1177/153537020322800812
  198. Prohaska J.R. Role of copper transporters in copper homeostasis. Am J Clin Nutr. 2008;88(3):826S–829S. doi: 10.1093/ajcn/88.3.826S
  199. Prudovsky I, Bagala C, Tarantini F, et al. The intracellular translocation of the components of the fibroblast growth factor 1 release complex precedes their assembly prior to export. J Cell Biol. 2002;158(2):201–208. doi: 10.1083/jcb.200203084
  200. Przybylkowski A, Cromadzka G, Chabik G, et al. Liver cirrhosis in patients newly diagnosed with neurological phenotype of Wilson’s disease. Funct Neurol. 2014;29(1):23–29.
  201. Pufahl RA, Singer CP, Peariso KL, et al. Metal ion chaperone function of the soluble Cu(I) receptor Atx1. Science. 1997;278(5339):853–856. doi: 10.1126/science.278.5339.853
  202. Puig S, Thiele DJ. Molecular mechanisms of copper uptake and distribution. Curr Opin Chem Biol. 2002;6(2):171–180. doi: 10.1016/s1367-5931(02)00298-3
  203. Qiu L, Ding X, Zhang Z, Kang YJ. Copper is required for cobalt-induced transcriptional activity of hypoxia-inducible factor-1. J Pharmacol Exp Ther. 2012;342(2):561–567. doi: 10.1124/jpet.112.194662
  204. Qin Z, Itoh S, Jeney V, et al. Essential role for the Menkes ATPase in activation of extracellular superoxide dismutase: implication for vascular oxidative stress. FASEB J. 2006;20(2):334–336. doi: 10.1096/fj.05-4564fje
  205. Ramos D, Mar D, Ishida M, et al. Mechanism of copper uptake from blood plasma ceruloplasmin by Mammalian cells. PLoS ONE. 2016;11(3):e0149516. doi: 10.1371/journal.pone.0149516
  206. Raju KS, Alessandri G, Ziche M, Gullino PM. Ceruloplasmin, copper ions, and angiogenesis. J Natl Cancer Inst. 1982;69(5):1183–1188.
  207. Redman BG, Esper P, Pan Q, et al. Phase II trial of tetrathiomolybdate in patients with advanced kidney cancer. Clin Cancer Res. 2003;9(5):1666–1672.
  208. Rezaei A, Khanamani Falahati-Pour S, Mohammadizadeh F, et al. Effect of a copper (II) complex on the induction of apoptosis in human hepatocellular carcinoma cells. Asian Pac J Cancer Prev. 2018;19(10):2877–2884. doi: 10.22034/APJCP.2018.19.10.2877
  209. Roberts BR, Lim NKH, McAllum EJ, et al. Oral treatment with Cu(II)(atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis. J Neurosci. 2014;34(23):8021–8031. doi: 10.1523/JNEUROSCI.4196-13.2014
  210. Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362(6415):59–62. doi: 10.1038/362059a0
  211. Roos PM, Vesterberg O, Syversen T, et al. Metal concentrations in cerebrospinal fluid and blood plasma from patients with amyotrophic lateral sclerosis. Biol Trace Elem Res. 2013;151(2):159–170. doi: 10.1007/s12011-012-9547-x
  212. Royce PM, Camakaris J, Danks DM. Reduced lysyl oxidase activity in skin fibroblasts from patients with Menkes’ syndrome. Biochem J. 1980;192(2):579–586. doi: 10.1042/bj1920579
  213. clinicaltrials.gov [Internet]. Treatment continuation study for patients with ALS/MND Who completed study CMD-2019-001. 2020. [cited 21 November 2024]. Available from: https://ClinicalTrials.gov/show/NCT04313166
  214. Rowland EA, Snowden CK, Cristea IM. Protein lipoylation: an evolutionarily conserved metabolic regulator of health and disease. Curr Opin Chem Biol. 2018;42:76–85. doi: 10.1016/j.cbpa.2017.11.003
  215. Russell K, Gillanders LK, Orr DW, Plank LD. Dietary copper restriction in Wilson’s disease. Eur J Clin Nutr. 2018;72(3):326–331. doi: 10.1038/s41430-017-0002-0
  216. Saleh SAK, Adly HM, Abdelkhaliq AA, Nassir AM. Serum levels of selenium, zinc, copper, manganese, and iron in prostate cancer patients. Curr Urol. 2020;14(1):44–49. doi: 10.1159/000499261
  217. Sarkar B, Lingertat-Walsh K, Clarke JT. Copper-histidine therapy for Menkes disease. J Pediatr. 1993;123(5);828–830. doi: 10.1016/s0022-3476(05)80870-4
  218. Scheinberg I. H, Sternlieb I. Wilson disease and idiopathic copper toxicosis. Am J Clin Nutr. 1996;63(5):842s–845s. doi: 10.1093/ajcn/63.5.842
  219. Schilsky ML, Czlonkowska A, Zuin M, et al. Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE): a randomised, open-label, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2022;7(12):1092–1102. doi: 10.1016/S2468-1253(22)00270-9
  220. Schilsky ML. Wilson disease: diagnosis, treatment, and follow-up. Clin Liver Dis. 2017;21(4):755–767. doi: 10.1016/j.cld.2017.06.011
  221. Schimmer AD. Clioquinol - a novel copper-dependent and independent proteasome inhibitor. Curr Cancer Drug Targets. 2011;11(3):325–331. doi: 10.2174/156800911794519770
  222. Schuschke DA, Saari JT, Miller FN. Leukocyte-endothelial adhesion is impaired in the cremaster muscle microcirculation of the copper-deficient rat. Immunol Lett. 2001;76(2):139–144. doi: 10.1016/S0165-2478 (01)00171-7
  223. Shanbhag V, Jasmer-McDonald K, Zhu S, et al. ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis. Proc Natl Acad Sci USA. 2019;116(14):6836–6841. doi: 10.1073/pnas.1817473116
  224. Sharma K, Mittal DK, Kesarwani RC, et al. Diagnostic prognostic significance of serum and tissue trace elements in breast malignancy. Indian J Med Sci. 1994;48(10):227–232.
  225. Sheline CT, Choi DW. Cu2+ toxicity inhibition of mitochondrial dehydrogenases in vitro and in vivo. Ann Neurol. 2004;55(5):645–653. doi: 10.1002/ana.20047
  226. Shen F, Cori WS, Li JL, et al. The association between serum levels of selenium, copper, and magnesium with thyroid cancer: a meta-analysis. Biol Trace Elem Res. 2015;167(2):225–235. doi: 10.1007/s12011-015-0304-9
  227. Shim H, Harris ZL. Genetic defects in copper metabolism. J Nutr. 2003;133(5 Suppl 1):1527S–1531S. doi: 10.1093/jn/133.5.1527S
  228. Shimada K, Reznik E, Stokes ME, et al. Copper-binding small molecule induces oxidative stress and cell-cycle arrest in glioblastoma-patient-derived cells. Cell Chem Biol. 2018;25(5): 585–594e587. doi: 10.1016/j.chembiol.2018.02.010
  229. Singh I, Sogare AP, Coma M, et al. Low levels of copper disrupt brain amyloid-beta homeostasis by altering its production and clearance. Proc Natl Acad Sci USA. 2013;110(36):14771–14776. doi: 10.1073/pnas.1302212110
  230. Sinha S, Taly AB, Ravishankar S, et al. Wilson’s disease: cranial MRI observations and clinical correlation. Neuroradiology. 2006;48(9);613–621. doi: 10.1007/s00234-006-0101-4
  231. Skrott Z, Mistrik M, Andersen KK, et al. Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4. Nature. 2017;552(7684):194–199. doi: 10.1038/nature25016
  232. Smirnova J, Kabin E, Järving I, et al. Copper(I)-binding properties of de-coppering drugs for the treatment of Wilson disease. alpha-Lipoic acid as a potential anti-copper agent. Sci Rep. 2018;8(1):1463. doi: 10.1038/s41598-018-19873-2
  233. Solmonson A, DeBerardinis RJ. Lipoic acid metabolism and mitochondrial redox regulation. J Biol Chem. 2018;293(20):7522–7530. doi: 10.1074/jbc.TM117.000259
  234. Son M, Pattaparthi K, Kawamata H, et al. Overexpression of CCS in G93A-SOD1 mice leads to accelerated neurological deficits with severe mitochondrial pathology. Proc Natl Acad Sci USA. 2007;104(14):6072–6077. doi: 10.1073/pnas.0610923104
  235. Soon CPW, Donnelly PS, Turner BJ, et al. Diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)) protects against peroxynitrite-induced nitrosative damage and prolongs survival in amyotrophic lateral sclerosis mouse model. J Biol Chem. 2011;286(51):44035–44044. doi: 10.1074/jbc.M111.274407
  236. Sozeri E, Feist D, Ruder H, Scharer K. Proteinuria and other renal functions in Wilson’s disease. Pediatr Nephrol. 1997;11(3):307–311. doi: 10.1007/s004670050282
  237. Starkebaum G, Harlan JM. Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. J Clin Investig. 1986;77(4):1370–1376. doi: 10.1172/JCI112442
  238. Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem. 1997;272(34):20963–20966. doi: 10.1074/jbc.272.34.20963
  239. Stockwell BR, Angeli JPF, Bayir H, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017;171(2):273–285. doi: 10.1016/j.cell.2017.09.021
  240. Squitti R, Simonelli I, Ventriglia M, et al. Meta-analysis of serum non-ceruloplasmin copper in Alzheimer’s disease. J Alzheimers Dis. 2014;38(4):809–822. doi: 10.3233/JAD-131247
  241. Squitti R, Lupoi D, Pasqualetti P, et al. Elevation of serum copper levels in Alzheimer’s disease. Neurology. 2002;59(8):1153–1161. doi: 10.1212/wnl.59.8.1153
  242. Sternlieb I, Quintana N, Volenberg I, Schilsky ML. An array of mitochondrial alterations in the hepatocytes of Long–Evans Cinnamon rats. Hepatology. 1995;22(6):1782–1787.
  243. Streltsov VA, Titmus SJ, Epa VC, et al. The structure of the amyloid-beta peptide high-affinity copper II binding site in Alzheimer disease. Biophys J. 2008:95(7):3447–3456. doi: 10.1529/biophysj.108.134429
  244. Sturtz LA, Diekert K, Jensen LT, et al. A fraction of yeast Cu,Zn-superoxide dismutase and its metallochaperone, CCS, localize to the intermembrane space of mitochondria. A physiological role for SOD1 in guarding against mitochondrial oxidative damage. J Biol Chem. 2001:276(41):38084–38089. doi: 10.1074/jbc.M105296200
  245. Sturrock A, Leavitt BR. The clinical and genetic features of Huntington disease. J Geriatr Psychiatry Neurol. 2010;23(4):243–259. doi: 10.1177/0891988710383573
  246. Swinnen B, Robberecht W. The phenotypic variability of amyotrophic lateral sclerosis. Nat Rev Neurol. 2014;10(11): 661–670. doi: 10.1038/nrneurol.2014.184
  247. Szauter KM, Cao T, Boyd CD, Csiszar K. Lysyl oxidase in development, aging and pathologies of the skin. Pathol Biol. (Paris). 2005;53(7):448–456. doi: 10.1016/j.patbio.2004.12.033
  248. Tafuri F, Ronchi D, Magri F, et al. SOD1 misplacing and mitochondrial dysfunction in amyotrophic lateral sclerosis pathogenesis. Front Cell Neurosci. 2015;9:336. doi: 10.3389/fncel.2015.00336
  249. Takahashi Y, Kako K, Kashiwabara SI, et al. Mammalian copper chaperone Cox17p has an essential role in activation of cytochrome C oxidase and embryonic development. Mol Cell Biol. 2002;22(21):7614–7621. doi: 10.1128/MCB.22.21.7614-7621.2002
  250. Tallaksen-Greene SJ, Janiszewska A, Benton K, et al. Evaluation of tetrathiomolybdate in the R6/2 model of Huntington disease. Neurosci Lett. 2009;452(1):60–62. doi: 10.1016/j.neulet.2009.01.040
  251. Tang X, Yan Z, Miao Y, et al. Copper in cancer: from limiting nutrient to therapeutic target. Front Oncology. 2023;13:1209156. doi: 10.3389/fonc2023.1209456
  252. Thiele DJ. Integrating trace element metabolism from the cell to the whole organism. J Nutr. 2003;133(5 Suppl 1):1579S–1580S. doi: 10.1093/jn/133.5.1579S
  253. Theophanides T, Anastassopoulou J. Copper and carcinogenesis. Crit Rev Oncol Hematol. (2002;42(1):57–64. doi: 10.1016/S1040-8428(02)00007-0
  254. Tiwari A, Liba A, Sohn SH, et al. Metal deficiency increases aberrant hydrophobicity of mutant superoxide dismutases that cause amyotrophic lateral sclerosis. J Biol Chem. 2009;284(40):27746–27758. doi: 10.1074/jbc.M109.043729
  255. Tokuda E, Ono S-I, Ishige K, et al. Ammonium tetrathiomolybdate delays onset, prolongs survival, and slows progression of disease in a mouse model for amyotrophic lateral sclerosis. Exp Neurol. 2008;213(1):122–128. doi: 10.1016/j.expneurol.2008.05.011
  256. Tokuda E, Okawa E, Ono S. Dysregulation of intracellular copper trafficking pathway in a mouse model of mutant copper/zinc superoxide dismutase-linked familial amyotrophic lateral sclerosis. J Neurochem. 2009;111(1):181–191. doi: 10.1111/j.1471-4159.2009.06310.x
  257. Tokuda E, Okawa E, Watanabe S, et al. Dysregulation of intracellular copper homeostasis is common to transgenic mice expressing human mutant superoxide dismutase-1s regardless of their copper-binding abilities. Neurobiol Dis. 2013;54:308–319. doi: 10.1016/j.nbd.2013.01.001
  258. Thrower JS, Hoffman L, Rechsteiner M, Pickart CM. Recognition of the polyubiquitin proteolytic signal. EMBO J. 2000;19(1):94–102. doi: 10.1093/emboj/19.1.94
  259. Tsang T, Posimo JM, Gudiel AA, et al. Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. Nat Cell Biol. 2020;22(4):412–424. doi: 10.1038/s41556-020-0481-4
  260. Tsvetkov P, Detappe A, Cai K, et al. Mitochondrial metabolism promotes adaptation to proteotoxic stress. Nat Chem Biol. 2019;15(7):681–689. doi: 10.1038/s41589-019-0291-9
  261. Tsvetkov PA, Coy S, Petrova B, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022;375(6586):1254–1261. doi: 10.1126/science.abf0529
  262. Turnlund JR, Keyes WR, Anderson HL, Acord LL. Copper absorption and retention in young men at three levels of dietary copper by use of the stable isotope 65Cu. Am J Clin Nutr. 1989;49(5):870–878. doi: 10.1093/ajcn/49.5.870
  263. Tumer Z, Moller LB. Menkes disease. Eur J Hum Genet. 2010;18(5):511–518. doi: 10.1038/ejhg.2009.187
  264. Turski ML, Bredy DS, Kim HJ, et al. A novel role for copper in Ras/mitogen-activated protein kinase signaling. Mol Cell Biol. 2012;32(7):1284–1295. doi: 10.1128/MCB.05722-11
  265. Vallieres C, Holland SL, Avery SV. Mitochondrial ferredoxin determines vulnerability of cells to copper excess. Cell Chem Biol. 2017;24(10):1228–1237.e3. doi: 10.1016/j.chembiol.2017.08.005
  266. Viola-Rhenals M, Patel KR, James-Santamaria L. et al. Recent advances in Antabuse (Disulfiram): the importance of its metal-binding ability to its anticancer activity. Curr Med Chem. 2018;25(4):506–524. doi: 10.2174/0929867324666171023161121
  267. Voli F, Vali E, Lerra L, et al. Intratumoral copper modulates PD-L1 expression and influences tumor immune evasion. Cancer Res. 2020;80(19):4129–4144. doi: 10.1158/0008-5472.CAN-20-0471
  268. Volker W, Unruh V, Dorszewski A, et al. Copper-induced inflammatory reactions of rat carotid arteries mimic restenosis/arteriosclerosis like neointima formation. Atherosclerosis. 1997;130(1-2):29–36. doi: 10.1016/s0021-9150(96)06039-x
  269. Voss K, Harris C, Ralle H, et al. Modulation of tau phosphorylation by environmental copper. Transl Neurodegener. 2014;3(1):24. doi: 10.1186/2047-9158-3-24
  270. Walshe JM. Penicillamine, a new oral therapy for Wilson v;s disease. Am J Med. 1956;21(4):487–495. doi: 10.1016/0002-9343(56)90066-3
  271. Wang D, Tian Z, Zhang P, et al. The molecular mechanisms of cuproptosis and its relevance to cardiovascular disease. Biomed Pharmacotherapy. 2023;163:4830. doi: 10.1016/j.biopha.2023.114830
  272. Wang Y, Li W, Patel SS, et al. Blocking the formation of radiation-induced breast cancer stem cells. Oncotarget. 2014;5(11):3743–3755. doi: 10.18632/oncotarget.1992
  273. Wang Q, Sun J, Chen T, et al. Ferroptosis, pyroptosis, and cuproptosis in alzheimer’s disease. ACS Chem Neurosci. 2023;14(19):3564–3587. doi: 10.1021/acschemneuro.3c00343
  274. Wang Y, Zhang L, Zhou F. Cuproptosis: a new form of programmed cell death. Cell Mol Immunology. 2022;19(8): 867–868. doi: 10.1038/s41423-022-00866-1
  275. Wang Z, Jin D, Zhou S, et al. Regulatory roles of copper metabolism and cuproptosis in human cancers. Front Oncol. 2023;13:1123420. doi: 10.3389/fonc.2023.1123420
  276. Wei H, Frei B, Beckman JS, Zhang WJ. Copper chelation by tetrathiomolybdate inhibits lipopolysaccharide-induced inflammatory responses in vivo. Am J Physiol Heart Circ Physiol. 2011;301(3): H712–H720. doi: 10.1152/ajpheart.01299.2010
  277. Wei H, Zhang WJ, McMillen TS, et al. Copper chelation by tetrathiomolybdate inhibits vascular inflammation and atherosclerotic lesion development in apolipoprotein E-deficient mice. Atherosclerosis. 2012;223(2):306–313. doi: 10.1016/j.atherosclerosis.2012.06.013
  278. Wei H, Zhang WJ, Leboeuf R, Frei B. Copper induces and copper chelation by tetrathiomolybdate inhibits endothelial activation in vitro. Redox Rep. 2014;19(1):40–48. doi: 10.1179/1351000213Y.0000000070
  279. Weiss KH, Thurik F, Gotthardt DN, et al. Efficacy and safety of oral chelators in treatment of patients with Wilson disease. Clin Gastroenterol Hepatol. 2013;11(8):1028–1035. doi: 10.1016/j.cgh.2013.03.012
  280. Weiss KH, Askari FK, Czlonkowska A, et al. Bis-choline tetrathiomolybdate in patients with Wilson’s disease: an open-label, multicentre, phase 2 study. Lancet Gastroenterol Hepatol. 2017;2(12):869–876. doi: 10.1016/S2468-1253(17)30293-5
  281. Williams JR, Trias E, Beiby PR, et al. Copper delivery to the CNS by CuATSM effectively treats motor neuron disease in SOD(G93A) mice co-expressing the Copper Chaperone-for-SOD. Neurobiol Dis. 2016;89:1–9. doi: 10.1016/j.nbd.2016.01.020.
  282. Wong W. Managed care considerations to improve health care utilization for patients with ALS. Am J Manag Care. 2023;29(7S):S120–S126. doi: 10.37765/ajmc.2023.89388
  283. Wu L, Meng F, Dong L, et al. Disulfiram and BKM120 in combination with chemotherapy impede tumor progression and delay tumor recurrence in tumor initiating cell-rich TNBC. Sci Rep. 2019;9(1):236. doi: 10.1038/s41598-018-35619-6
  284. Xie J, Yang Y, Gao Y, He J. Cuproptosis: mechanisms and links with cancer. Mol Cancer. 2023;22(1):46. doi: 10.1186/s12943-023-01732-y
  285. Xie Y, Hou W, Song X, et al. Ferroptosis: process and function. Cell Death Differ. 2016;23(3):369–379. doi: 10.1038/cdd.2015.158
  286. Xiao Y, Chen DI, Zhang X, et al. Molecular study on copper-mediated tumor proteasome inhibition and cell death. Int J Oncol. 2010;37(1):81–87. doi: 10.3892/ijo_00000655
  287. Xu Y, Liu SY, Zeng L, et al. Enzyme-engineered nonporous copper(I) coordination polymer nanoplatform for cuproptosis-based synergistic cancer therapy. Adv Mater. 2022;34(43):e2204733, doi: 10.1002/adma.202204733
  288. Yadav D, Lee JY, Puranik N, et al. Modulating the ubiquitin–proteasome system: a therapeutic strategy for autoimmune diseases. Cell. 2022;11(7):1093. doi: 10.3390/cells11071093
  289. Yaman M, Kaya G, Simsek M. Comparison of trace element concentrations in cancerous and noncancerous human endometrial and ovary tissues. Int J Gynecol Cancer. 2007;17(1):220–228. doi: 10.1111/j.1525-1438.2006.00742.x
  290. Yan R, Xie E, Li Y, et al. The structure of erastin-bound xCT-4F2hc complex reveals molecular mechanisms underlying erastin-induced ferroptosis. Cell Res. 2022;32(7):687–690. doi: 10.1038/s41422-022-00642-w
  291. Yan HF, Zou T, Tuo Q-Z, et al. Ferroptosis: mechanisms and links with diseases. Signal Transduct Target Ther. 2021;6(1):49. doi: 10.1038/s41392-020-00428-9
  292. Yang H, Chen X, Li K, et al. Repurposing old drugs as new inhibitors of the ubiquitin–proteasome pathway for cancer treatment. Semin Cancer Biol. 2021;68:105–122. doi: 10.1016/j.semcancer.2019.12.013
  293. Yoshii J, Yoshiji H, Kuriyama S, et al. The copper-chelating agent, trientine, suppresses tumor development and angiogenesis in the murine hepatocellular carcinoma cells. Int J Cancer. 2001;94(6):768–773. doi: 10.1002/ijc.1537
  294. Yu Y, Jiang L, Wang H, et al. Hepatic transferrin plays a role in systemic iron homeostasis and liver ferroptosis. Blood. 2020;136(6):726–739. doi: 10.1182/blood.2019002907
  295. Zhang H, Chen D, Ringler J, et al. Disulfiram treatment facilitates phosphoinositide 3-kinase inhibition in human breast cancer cells in vitro and in vivo. Cancer Res. 2010;70(10):3996–4004. doi: 10.1158/0008-5472.CAN-09-3752
  296. Zheng J, Conrad M. The metabolic underpinnings of ferroptosis. Cell Metab. 2020;32(6):920–937. doi: 10.1016/j.cmet.2020.10.011
  297. Zheng P, Zhou C, Lu L, et al. Elesclomol: a copper ionophore targeting mitochondrial metabolism for cancer therapy. J Exp Clin Cancer Res. 2022;41:271. doi: 10.1186/s13046-022-02485-0
  298. Zhuo X, Liu Z, Aishajiang R, et al. Recent progress of copper-based nanomaterials in tumor-targeted photothermal therapy/photodynamic therapy. Pharmaceutics. 2023;15(9):2293. doi: 10.3390/pharmaceutics15092293

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar
2. Fig. 1. Copper ion cellular and mitochondrial metabolic transport pathways (adapted from Chen et al. [50]). CP — ceruloplasmin; MT — metallothionein; CTR1 — copper ion transmembrane transporter; CCS and SOD1 — copper chaperones delivering copper ions to subcellular compartments, including mitochondria, nucleus, and Golgi apparatus; CCO — mitochondrial complex containing COX17, COX11, SCO1, SCO2 (intramitochondrial copper ion transporters); GSN — glutathione; ATOX1 — Cu+ ion transporter [183]

Baixar (501KB)
Metadados
3. Fig. 2. Mechanism of elesclomol-induced cuproptosis (adapted from Chen et al. [51]). TTM — tetrathiomolybdate; FDX1 — ferredoxin; LIAS — lipoate synthase, regulator of Krebs cycle protein lipoylation; LPK — mitochondrial lipoylation enzyme [261]

Baixar (1MB)
Metadados
4. Fig. 3. Mitochondrial disruptions in cuproptosis (adapted from Zheng et al. [297]). FDX1 — ferredoxin 1; LA — lipoic acid; DLAT — dihydrolipoamide S-acetyltransferase; LIAS — lipoate synthase; PDH — pyruvate dehydrogenase complex; Cyt c — cytochrome C; Fe-S — iron-sulfur protein clusters; CoQ — coenzyme Q; ETC — electron transport chain

Baixar (451KB)
Metadados
5. Fig. 4. Lipoylation scheme of pyruvate dehydrogenase complex subunits in the krebs cycle (adapted from Mayr et al. [165]). CoA — coenzyme A; LA — lipoic acid; SH — sulfide bonds; TPP — thiamine pyrophosphate

Baixar (561KB)
Metadados
6. Fig. 5. Ubiquitin-proteasome protein degradation system (adapted from Aliabady et al. [14]). Ub — ubiquitin; PPi — pyrophosphate; E1 — ubiquitin-activating enzymes; E2 — ubiquitin-conjugating enzymes; E3 — ubiquitin-ligating enzymes

Baixar (515KB)
Metadados
7. Fig. 6. Structural formula of the elesclomol-copper complex

Baixar (140KB)
Metadados
8. Fig. 7. Therapeutic strategies using cuproptosis modulators for cancer treatment (adapted from Kang et al. [125]). DSF — disulfiram; Cu — copper; CuET — Cu-diethyldithiocarbamate

Baixar (411KB)
Metadados

Declaração de direitos autorais © Eco-Vector, 2024

Link à descrição da licença: https://eco-vector.com/for_authors.php#07
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 84654 от 01.02.2023 г.