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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]
Copyright of Annual Review of Neuroscience is the property of Annual Reviews Inc. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: <searchLink fieldCode="AR" term="%22Sheehan%2C+Garrett+D%2E%22">Sheehan, Garrett D.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ding%2C+Jun+B%2E%22">Ding, Jun B.</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Annual+Review+of+Neuroscience%22">Annual Review of Neuroscience</searchLink>. Jul2026, Vol. 49 Issue 1, p273-288. 12p.
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  Data: 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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  Data: <i>Copyright of Annual Review of Neuroscience is the property of Annual Reviews Inc. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1146/annurev-neuro-112723-051616
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      – Code: eng
        Text: English
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        PageCount: 12
        StartPage: 273
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      – SubjectFull: Alpha-synuclein
        Type: general
      – SubjectFull: Neural physiology
        Type: general
      – SubjectFull: Extracellular vesicles
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      – SubjectFull: Synaptic vesicles
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      – SubjectFull: Synapses
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      – SubjectFull: Neural transmission
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      – SubjectFull: Protein-protein interactions
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      – TitleFull: Synucleins in Neural Physiology: Understanding Endogenous Function to Better Contextualize Pathology.
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              Text: Jul2026
              Type: published
              Y: 2026
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