Title | α-Synuclein in synaptic function and dysfunction. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Sharma M, Burré J |
Journal | Trends Neurosci |
Volume | 46 |
Issue | 2 |
Pagination | 153-166 |
Date Published | 2023 Feb |
ISSN | 1878-108X |
Keywords | alpha-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. |
DOI | 10.1016/j.tins.2022.11.007 |
Alternate Journal | Trends Neurosci |
PubMed ID | 36567199 |
PubMed Central ID | PMC9877183 |
Grant List | R35 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 |