Physiological roles of α-synuclein serine-129 phosphorylation - not an oxymoron.

IF 14.6 1区 医学 Q1 NEUROSCIENCES Trends in Neurosciences Pub Date : 2024-07-01 Epub Date: 2024-06-10 DOI:10.1016/j.tins.2024.05.005
Nagendran Ramalingam, Christian Haass, Ulf Dettmer
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Abstract

α-Synuclein (αS) is an abundant presynaptic protein that regulates neurotransmission. It is also a key protein implicated in a broad class of neurodegenerative disorders termed synucleinopathies, including Parkinson's disease (PD) and Lewy body dementia (LBD). Pathological αS deposits in these diseases, Lewy bodies (LBs)/neurites (LNs), contain about 90% of αS in its phospho-serine129 (pS129) form. Therefore, pS129 is widely used as a surrogate marker of pathology. However, recent findings demonstrate that pS129 is also physiologically triggered by neuronal activity to positively regulate synaptic transmission. In this opinion article, we contrast the literature on pathological and physiological pS129, with a special focus on the latter. We emphasize that pS129 is ambiguous and knowledge about the context is necessary to correctly interpret changes in pS129.

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α-突触核蛋白丝氨酸-129磷酸化的生理作用--并非矛盾论。
α-突触核蛋白(αS)是一种丰富的突触前蛋白,可调节神经传递。它也是一类神经退行性疾病(包括帕金森病(PD)和路易体痴呆症(LBD))中的关键蛋白。这些疾病的病理αS沉积物路易体(LBs)/神经元(LNs)中约有90%的αS以磷酸丝氨酸129(pS129)的形式存在。因此,pS129 被广泛用作病理学的替代标志物。然而,最近的研究结果表明,pS129 在生理上也会被神经元活动触发,从而积极调节突触传递。在这篇观点文章中,我们对比了有关病理和生理 pS129 的文献,并特别关注后者。我们强调,pS129 是模糊的,要正确解读 pS129 的变化,必须了解相关的背景知识。
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来源期刊
Trends in Neurosciences
Trends in Neurosciences 医学-神经科学
CiteScore
26.50
自引率
1.30%
发文量
123
审稿时长
6-12 weeks
期刊介绍: For over four decades, Trends in Neurosciences (TINS) has been a prominent source of inspiring reviews and commentaries across all disciplines of neuroscience. TINS is a monthly, peer-reviewed journal, and its articles are curated by the Editor and authored by leading researchers in their respective fields. The journal communicates exciting advances in brain research, serves as a voice for the global neuroscience community, and highlights the contribution of neuroscientific research to medicine and society.
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