α-Synuclein in synaptic function and dysfunction.

Titleα-Synuclein in synaptic function and dysfunction.
Publication TypeJournal Article
Year of Publication2023
AuthorsSharma M, Burré J
JournalTrends Neurosci
Volume46
Issue2
Pagination153-166
Date Published2023 Feb
ISSN1878-108X
Keywordsalpha-Synuclein, Humans, Neurotransmitter Agents, Parkinson Disease, Synaptic Vesicles, Synucleinopathies
Abstract

α-Synuclein is a neuronal protein that is enriched in presynaptic terminals. Under physiological conditions, it binds to synaptic vesicle membranes and functions in neurotransmitter release, although the molecular details remain unclear, and it is controversial whether α-synuclein inhibits or facilitates neurotransmitter release. Pathologically, in synucleinopathies including Parkinson's disease (PD), α-synuclein forms aggregates that recruit monomeric α-synuclein and spread throughout the brain, which triggers neuronal dysfunction at molecular, cellular, and organ levels. Here, we present an overview of the effects of α-synuclein on SNARE-complex assembly, neurotransmitter release, and synaptic vesicle pool homeostasis, and discuss how the observed divergent effects of α-synuclein on neurotransmitter release can be reconciled. We also discuss how gain-of-function versus loss-of-function of α-synuclein may contribute to pathogenesis in synucleinopathies.

DOI10.1016/j.tins.2022.11.007
Alternate JournalTrends Neurosci
PubMed ID36567199
PubMed Central IDPMC9877183
Grant ListR35 GM128837 / GM / NIGMS NIH HHS / United States
RF1 NS126342 / NS / NINDS NIH HHS / United States
R01 NS102181 / NS / NINDS NIH HHS / United States
R01 NS121077 / NS / NINDS NIH HHS / United States
R21 AG061600 / AG / NIA NIH HHS / United States
R01 NS113960 / NS / NINDS NIH HHS / United States
R01 AG052505 / AG / NIA NIH HHS / United States
R01 NS095988 / NS / NINDS NIH HHS / United States
R21 NS127939 / NS / NINDS NIH HHS / United States
F31 NS125949 / NS / NINDS NIH HHS / United States