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

Since the initial identification of alpha-synuclein (α-syn) at the synapse, numerous studies demonstrated that α-syn is a key player in the etiology of Parkinson's disease (PD) and other synucleinopathies. Recent advances underline interactions between α-syn and lipids that also participate in...

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Published in:Cells (Basel, Switzerland) Switzerland), 2021-09, Vol.10 (9), p.2452
Main Authors: Sarchione, Alessia, Marchand, Antoine, Taymans, Jean-Marc, Chartier-Harlin, Marie-Christine
Format: Article
Language:English
Subjects:
alpha-Synuclein - metabolism
Alzheimer's disease
Animals
Dopamine
Epigenetics
Etiology
Exocytosis
genetics
Homeostasis
Humans
Immune system
Lipid membranes
Lipid metabolism
Lipids
Lipids - adverse effects
Lipids - analysis
Lipids - physiology
Membranes
Movement disorders
Mutation
Neurodegeneration
Neurodegenerative diseases
Parkinson disease
Parkinson Disease - etiology
Parkinson Disease - pathology
Parkinson's disease
Pathogenesis
Proteins
Review
Synuclein
Synucleinopathies - etiology
Synucleinopathies - pathology
α-synuclein
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Summary:Since the initial identification of alpha-synuclein (α-syn) at the synapse, numerous studies demonstrated that α-syn is a key player in the etiology of Parkinson's disease (PD) and other synucleinopathies. Recent advances underline interactions between α-syn and lipids that also participate in α-syn misfolding and aggregation. In addition, increasing evidence demonstrates that α-syn plays a major role in different steps of synaptic exocytosis. Thus, we reviewed literature showing (1) the interplay among α-syn, lipids, and lipid membranes; (2) advances of α-syn synaptic functions in exocytosis. These data underscore a fundamental role of α-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 α-syn on lipid metabolism, modulation of α-syn levels by lipids, as well as the identification of genetic determinants involved in lipid homeostasis associated with α-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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10092452