Membrane and Cell BiologyMembrane and Cell BiologyБиологические мембраны0233-47553034-5219The Russian Academy of Sciences66741510.31857/S0233475524050021cbxvmaОБЗОРЫReview ArticleAlterations in store-operated calcium entry in neurodegenerative pathologies: history, facts, perspectivesНарушения депо-управляемого входа кальция при нейродегенеративных патологиях: история, факты, перспективыVigontV. A.ВигонтВ. А.
Russian Federation
evkazn@incras.ruKaznacheyevaE. V.КазначееваЕ. В.
Russian Federation
evkazn@incras.ruInstitute of cytology, Russian Academy of SciencesИнститут цитологии РАН04112024415-636838226022025Copyright ©; 2024, The Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024The Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0233-4755/article/view/667415

Neurodegenerative disorders, along with cardiovascular and oncological pathologies, are one of the most actual issues facing modern medicine. Therefore, the study of the molecular mechanisms of their pathogenesis and the search for new drug targets is highly demanded. Neuronal calcium signalling has attracted close attention, as altered calcium homeostasis has been demonstrated in the pathogenesis of various neurodegenerative diseases. In this review, we focus on one of the most ubiquitous and important pathways for calcium uptake: store-operated calcium entry. Here we describe studies demonstrating disturbances in store-operated calcium entry in various neurodegenerative pathologies, including Alzheimer’s, Parkinson’s and Huntington’s diseases. Also, we analyse the molecular determinants underlying these disturbances and propose ways for pharmacological correction of altered calcium signaling. The information summarized in the review will allow us to consider store-operated calcium channels as promising targets for the drug development in order to treat neurodegenerative pathologies and outline further promising directions for the investigation.

Нейродегенеративные заболевания, наряду с сердечно-сосудистыми и онкологическими патологиями, являются одной из наиболее острых проблем современной медицины, требующих комплексного подхода к изучению молекулярных механизмов их патогенеза и поиску новых мишеней для терапевтического воздействия. Пристального внимания исследователей заслуживает нейрональная кальциевая сигнализация, многочисленные нарушения которой были отмечены при изучении ряда нейродегенеративных патологий. В данном обзоре мы сфокусировались на одном из наиболее общих и важных путей поступления кальция в клетку: входе кальция через депо-управляемые каналы плазматической мембраны. Здесь собраны исследования, демонстрирующие нарушения депо-управляемого входа кальция при различных нейродегенеративных заболеваниях, прежде всего, при болезнях Альцгеймера, Паркинсона и Хантингтона, проанализированы молекулярные детерминанты, опосредующие данные нарушения, предложены пути их фармакологической коррекции. Обобщенная в обзоре информация позволит взглянуть на депо-управляемые каналы как на одну из наиболее перспективных мишеней в поиске новых терапевтических агентов для борьбы с нейродегенеративными патологиями и наметить дальнейшие перспективные направления исследований в данной области.

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