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Increased Expression of α-Synuclein Reduces Neurotransmitter Release by Inhibiting Synaptic Vesicle Reclustering after Endocytosis by Venu M. Nemani; Wei Lu; Victoria Berge; Ken Nakamura; Bibiana Onoa; Michael K. Lee; Farrukh A. Chaudhry; Roger A. Nicoll; Robert H. Edwards is a Neuroscience article available to read on EtoBox.
What is Increased Expression of α-Synuclein Reduces Neurotransmitter Release by Inhibiting Synaptic Vesicle Reclustering after Endocytosis about?
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 overexpression 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.
Who reads Increased Expression of α-Synuclein Reduces Neurotransmitter Release by Inhibiting Synaptic Vesicle Reclustering after Endocytosis?
It is typically read by researchers, students, and practitioners in Neuroscience.
- Author
- Venu M. Nemani; Wei Lu; Victoria Berge; Ken Nakamura; Bibiana Onoa; Michael K. Lee; Farrukh A. Chaudhry; Roger A. Nicoll; Robert H. Edwards
- Publisher
- Elsevier BV
- Published
- 2010
- Language
- EN
- Field
- Neuroscience (Life Sciences)