α‐Synuclein produces a long‐lasting increase in neurotransmitter release
Open accessAbstract
Wild-type alpha-synuclein, a protein of unknown function, has received much attention because of its involvement in a series of diseases that are known as synucleinopathies. We find that long-lasting potentiation of synaptic transmission between cultured hippocampal neurons is accompanied by an increase in the number of alpha-synuclein clusters. Conversely, suppression of alpha-synuclein expression through antisense nucleotide and knockout techniques blocks the potentiation, as well as the glutamate-induced increase in presynaptic functional bouton number. Consistent with these findings, alpha-synuclein introduction into the presynaptic neuron of a pair of monosynaptically connected cells causes a rapid and long-lasting enhancement of synaptic transmission, and rescues the block of potentiation in alpha-synuclein null mouse cultures. Also, we report that the application of nitric oxide (NO) increases the number of alpha-synuclein clusters, and inhibitors of NO-synthase block this increase, supporting the hypothesis that NO is involved in the enhancement of the number of alpha-synuclein clusters. Thus, alpha-synuclein is involved in synaptic plasticity by augmenting transmitter release from the presynaptic terminal.
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αSyn is predominantly expressed within the presynaptic terminals of neurons.
“αSyn is predominantly expressed within the presynaptic terminals of neurons [141–143]”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [143]
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- Authors
- Liu, S., Ninan, I., Antonova, I., Battaglia, F., Trinchese, F., Narasanna, A., Kolodilov, N., Dauer, W., Hawkins, R. D., & Arancio, O.
- Affiliations
- Columbia University (US)
- Corresponding author
- Arancio, Ottavio
- ORCID
- Venue
- The EMBO Journal
- Published
- 2004-10-28
- Volume
- 23
- Issue
- 22
- Pages
- 4506-4516
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC526467
- OpenAlex
- W1965573624
- Cited by
- 198
- References
- 35
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 9 · 2023: 6 · 2022: 11 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 12 · 2016: 7 · 2015: 14 · 2014: 8 · 2013: 10 · 2012: 12
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Whitehall Foundation
- University of Pennsylvania
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS040045, NS 40045)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- alpha-synuclein, neurotransmitter release, synaptic potentiation, synaptic plasticity, synucleinopathies, hippocampal neurons, presynaptic terminals, nitric oxide, nitric oxide synthase, antisense knockdown, knockout mice, glutamate
- MeSH terms
- Animals, Animals, Newborn, Cells, Cultured, Electrophysiology, Endocytosis, Enzyme Inhibitors, Exocytosis, Hippocampus, Immunohistochemistry, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Nitric Oxide, Recombinant Fusion Proteins, Synapses, Blotting, Western, Oligonucleotides, Antisense, Mice, Knockout, Patch-Clamp Techniques, Nitric Oxide Synthase, Mice, Rats, Synucleins, alpha-Synuclein
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