Alpha-Synuclein and Lipids: The Elephant in the Room?

被引：39

作者：

Sarchione, Alessia ^{[1
]}

Marchand, Antoine ^{[1
]}

Taymans, Jean-Marc ^{[1
]}

Chartier-Harlin, Marie-Christine ^{[1
]}

机构：

[1] Univ Lille, INSERM, CHU Lille, UMR S 1172,Li1NCog,Lille Neurosci & Cognit, F-59000 Lille, France

来源：

CELLS | 2021年 / 10卷 / 09期

关键词：

alpha-synuclein; exocytosis; genetics; lipids; membranes; Parkinson disease; SNARE complex; synapse; vesicle fusion; therapeutic target; GENOME-WIDE ASSOCIATION; STRIATAL DOPAMINE RELEASE; STEAROYL-COA DESATURASE; PARKINSONS-DISEASE; MICE LACKING; CSP-ALPHA; MITOCHONDRIAL DYSFUNCTION; MEMBRANE INTERACTIONS; SYNAPTIC FUNCTION; CHROMAFFIN CELLS;

D O I：

10.3390/cells10092452

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Since the initial identification of alpha-synuclein (alpha-syn) at the synapse, numerous studies demonstrated that alpha-syn is a key player in the etiology of Parkinson's disease (PD) and other synucleinopathies. Recent advances underline interactions between alpha-syn and lipids that also participate in alpha-syn misfolding and aggregation. In addition, increasing evidence demonstrates that alpha-syn plays a major role in different steps of synaptic exocytosis. Thus, we reviewed literature showing (1) the interplay among alpha-syn, lipids, and lipid membranes; (2) advances of alpha-syn synaptic functions in exocytosis. These data underscore a fundamental role of alpha-syn/lipid interplay that also contributes to synaptic defects in PD. The importance of lipids in PD is further highlighted by data showing the impact of alpha-syn on lipid metabolism, modulation of alpha-syn levels by lipids, as well as the identification of genetic determinants involved in lipid homeostasis associated with alpha-syn pathologies. While questions still remain, these recent developments open the way to new therapeutic strategies for PD and related disorders including some based on modulating synaptic functions.

引用

页数：37

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