The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Increased Expression of α-Synuclein Reduces Neurotransmitter Release by Inhibiting Synaptic Vesicle Reclustering after Endocytosis
Open accessAbstract
Summary The protein α-synuclein accumulates in the brain of patients with sporadic Parkinson’s disease (PD), and increased gene dosage causes a severe, dominantly inherited form of PD, but we know little about the effects of synuclein that precede degeneration. α-Synuclein localizes to the nerve terminal, but the knockout has little if any effect on synaptic transmission. In contrast, we now find that the modest over-expression of α-synuclein, in the range predicted for gene multiplication and in the absence of overt toxicity, markedly inhibits neurotransmitter release. The mechanism, elucidated by direct imaging of the synaptic vesicle cycle, involves a specific reduction in size of the synaptic vesicle recycling pool. Ultrastructural analysis demonstrates reduced synaptic vesicle density at the active zone, and imaging further reveals a defect in the reclustering of synaptic vesicles after endocytosis. Increased levels of α-synuclein thus produce a specific, physiological defect in synaptic vesicle recycling that precedes detectable neuropathology.
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Cites
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Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
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Self-citation
Cited by
Volpicelli-Daley, L. A., Luk, K. C., Patel, T. P., Tanik, S. A., Riddle, D. M., Stieber, A., Meaney, D. F., Trojanowski, J. Q., & Lee, V. M.-Y. (2011) · Neuron · doi:10.1016/j.neuron.2011.08.033 · Cited by 1,569
-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446
α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies
Wong, Y. C., & Krainc, D. (2017) · Nature Medicine · doi:10.1038/nm.4269 · Cited by 897
Bendor, J. T., Logan, T. P., & Edwards, R. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.004 · Cited by 825
Self-citationLipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation
Galvagnion, C., Buell, A. K., Meisl, G., Michaels, T. C. T., Vendruscolo, M., Knowles, T. P. J., & Dobson, C. M. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1750 · Cited by 661
Metadata
- Authors
- Nemani, V. M., Lu, W., Berge, V., Nakamura, K., Onoa, B., Lee, M. K., Chaudhry, F. A., Nicoll, R. A., & Edwards, R. H.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 65
- Issue
- 1
- Pages
- 66-79
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2009573330
- Cited by
- 1,056
- References
- 15
- FWCI
- 43.24
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Nemani, V. M., Lu, W., Berge, V., Nakamura, K., Onoa, B., Lee, M. K., Chaudhry, F. A., Nicoll, R. A., & Edwards, R. H. (2010). Increased Expression of α-Synuclein Reduces Neurotransmitter Release by Inhibiting Synaptic Vesicle Reclustering after Endocytosis. Neuron. https://doi.org/10.1016/j.neuron.2009.12.023
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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
