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Synucleins in Neural Physiology: Understanding Endogenous Function to Better Contextualize Pathology.

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Title: Synucleins in Neural Physiology: Understanding Endogenous Function to Better Contextualize Pathology.
Authors: Sheehan, Garrett D. (AUTHOR), Ding, Jun B. (AUTHOR)
Source: Annual Review of Neuroscience. Jul2026, Vol. 49 Issue 1, p273-288. 12p.
Subjects: Alpha-synuclein, Neural physiology, Extracellular vesicles, Synaptic vesicles, Synapses, Neural transmission, Protein-protein interactions
Abstract: Perhaps most well-known for its penetrant role in synucleinopathies, alpha-synuclein's nonpathological function remains incompletely characterized. Most widely regarded as a putative presynaptic protein, a growing body of work over the last few decades demonstrates that alpha-synuclein participates in a broad and more diverse set of neuronal functions. Alpha-synuclein is a small, intrinsically disordered protein comprising three functionally distinct regions that mediate membrane binding, vesicle clustering, and protein-protein interactions. At synapses, alpha-synuclein participates in multiple steps of neurotransmission, including organization of the vesicle reserve pool, recruitment of release machinery, and recycling of synaptic vesicles. Emerging evidence further supports roles for alpha-synuclein beyond classical presynaptic compartments, including interactions with nonsynaptic membranes and secretion via extracellular vesicles. This review aims to integrate the literature on alpha-synuclein's structure and function to better underscore how these properties may contribute to vulnerability in disease when these normal functions are lost. [ABSTRACT FROM AUTHOR]
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Database: Psychology and Behavioral Sciences Collection
Description
Abstract:Perhaps most well-known for its penetrant role in synucleinopathies, alpha-synuclein's nonpathological function remains incompletely characterized. Most widely regarded as a putative presynaptic protein, a growing body of work over the last few decades demonstrates that alpha-synuclein participates in a broad and more diverse set of neuronal functions. Alpha-synuclein is a small, intrinsically disordered protein comprising three functionally distinct regions that mediate membrane binding, vesicle clustering, and protein-protein interactions. At synapses, alpha-synuclein participates in multiple steps of neurotransmission, including organization of the vesicle reserve pool, recruitment of release machinery, and recycling of synaptic vesicles. Emerging evidence further supports roles for alpha-synuclein beyond classical presynaptic compartments, including interactions with nonsynaptic membranes and secretion via extracellular vesicles. This review aims to integrate the literature on alpha-synuclein's structure and function to better underscore how these properties may contribute to vulnerability in disease when these normal functions are lost. [ABSTRACT FROM AUTHOR]
ISSN:0147006X
DOI:10.1146/annurev-neuro-112723-051616