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J Neurochem. 2019 Sep;150(5):475-486. doi: 10.1111/jnc.14810. Epub 2019 Jul 28.

The physiological role of α-synuclein and its relationship to Parkinson's Disease.

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Departments of Psychiatry, Neurology and Pharmacology, Columbia University Medical Center, New York State Psychiatric Institute.
Departments of Neurology and Physiology, Graduate Programs in Cell Biology, Biomedical Sciences and Neuroscience, UCSF School of Medicine.


The protein α-synuclein has a central role in the pathogenesis of Parkinson's disease (PD). In this review, we discuss recent results concerning its primary function, which appears to be on cell membranes. The pre-synaptic location of synuclein has suggested a role in neurotransmitter release and it apparently associates with synaptic vesicles because of their high curvature. Indeed, synuclein over-expression inhibits synaptic vesicle exocytosis. However, loss of synuclein has not yet been shown to have a major effect on synaptic transmission. Consistent with work showing that synuclein can promote as well as sense membrane curvature, recent analysis of synuclein triple knockout mice now shows that synuclein accelerates dilation of the exocytic fusion pore. This form of regulation affects primarily the release of slowly discharged lumenal cargo such as neural peptides, but presumably also contributes to maintenance of the release site. This article is part of the Special Issue "Synuclein".


Lewy pathology; Parkinson's disease; fusion pore; regulated exocytosis; synaptic vesicle; synuclein

[Available on 2020-09-01]

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