Search and analysis of mutations affecting the aggregation of amyloid beta peptides
- Authors: Malikova O.A.1, Zobnina A.E.1, Kachkin D.V.1, Aksenova A.Y.1, Chernoff Y.O.2, Rubel A.A.1
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Affiliations:
- Saint Petersburg State University
- School of Biological Sciences, Georgia Institute of Technology
- Issue: Vol 20 (2022): Supplement
- Pages: 53-53
- Section: Genetically modified organism. The Нistory, Achivements, Social and Environmental Riscs
- URL: https://journals.eco-vector.com/ecolgenet/article/view/112356
- DOI: https://doi.org/10.17816/ecogen112356
- ID: 112356
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Abstract
Alzheimer’s disease (AD) is a fatal neurodegenerative disorder and the most common form of dementia in late life. According to the generally accepted hypothesis, the main cause of AD is the aggregation of the amyloid beta (Aβ) peptide which leads to the formation and accumulation of plaques around a brain cells. Aβ isoform that prevails in plaques consists of 42 amino acid residues and is termed Aβ42. Here, we apply the yeast-based assay for searching mutations that affecting human Aβ42 peptide aggregation. This assay is based on phenotypic detection of amyloid aggregation, nucleated by the attachment of Aβ to prion domain of the yeast protein Sup35 in yeast S. cerevisiae (Chandramowlishwaran et al. 2018 J. Biol. Chem. 293:3436). As a result of screening, 70 derivatives with single or multiple mutations, altering amyloid nucleation were identified. Effects of most interesting mutations on biochemical and cytological parameters of Aβ aggregates, as well on the Aβ amyloid structure have been investigated. Results of these experiments shed light on modes and pathways of Aβ aggregation.
This study was supported by grant 20-14-00148 from Russian Science Foundation and by St. Petersburg State University (project 93025998). Authors acknowledge SPbSU Resource Centers “Chromas”, “Molecular and Cell Technologies”, and “Biobank”.
Full Text
Alzheimer’s disease (AD) is a fatal neurodegenerative disorder and the most common form of dementia in late life. According to the generally accepted hypothesis, the main cause of AD is the aggregation of the amyloid beta (Aβ) peptide which leads to the formation and accumulation of plaques around a brain cells. Aβ isoform that prevails in plaques consists of 42 amino acid residues and is termed Aβ42. Here, we apply the yeast-based assay for searching mutations that affecting human Aβ42 peptide aggregation. This assay is based on phenotypic detection of amyloid aggregation, nucleated by the attachment of Aβ to prion domain of the yeast protein Sup35 in yeast S. cerevisiae (Chandramowlishwaran et al. 2018 J. Biol. Chem. 293:3436). As a result of screening, 70 derivatives with single or multiple mutations, altering amyloid nucleation were identified. Effects of most interesting mutations on biochemical and cytological parameters of Aβ aggregates, as well on the Aβ amyloid structure have been investigated. Results of these experiments shed light on modes and pathways of Aβ aggregation.
This study was supported by grant 20-14-00148 from Russian Science Foundation and by St. Petersburg State University (project 93025998). Authors acknowledge SPbSU Resource Centers “Chromas”, “Molecular and Cell Technologies”, and “Biobank”.
About the authors
Oksana A. Malikova
Saint Petersburg State University
Author for correspondence.
Email: oks_malik@mail.ru
SPIN-code: 6695-7314
Junior Researcher, Laboratory of Amyloid Biology
Russian Federation, Saint PetersburgAnastasia E. Zobnina
Saint Petersburg State University
Email: agrad74@mail.ru
SPIN-code: 6157-1651
PhD, Senior Researcher, Laboratory of Amyloid Biology
Russian Federation, Saint PetersburgDaniel V. Kachkin
Saint Petersburg State University
Email: pspdaniel@mail.ru
SPIN-code: 4823-8619
Junior Researcher, Laboratory of Amyloid Biology
Russian Federation, Saint PetersburgAnna Yu. Aksenova
Saint Petersburg State University
Email: aksena@gmail.com
SPIN-code: 4914-7675
PhD, Senior Researcher, Laboratory of Amyloid Biology
Russian Federation, Saint PetersburgYury O. Chernoff
School of Biological Sciences, Georgia Institute of Technology
Email: yury.chernoff@gmail.com
SPIN-code: 6201-0359
PhD, School of Biological Sciences
United States, Atlanta, GeorgiaAleksandr A. Rubel
Saint Petersburg State University
Email: arubel@mail.ru
SPIN-code: 3961-4690
PhD, Head of the Laboratory, Laboratory of Amyloid Biology
Russian Federation, Saint Petersburg