Double-knockout mice for α- and β-synucleins: Effect on synaptic functions
Open accessAbstract
An abundant presynaptic protein, α-synuclein, is centrally involved in the pathogenesis of Parkinson's disease. However, conflicting data exist about the normal function of α-synuclein, possibly because α-synuclein is redundant with the very similar β-synuclein. To investigate the functions of synucleins systematically, we have now generated single- and double-knockout (KO) mice that lack α- and/or β-synuclein. We find that deletion of synucleins in mice does not impair basic brain functions or survival. We detected no significant changes in the ultrastructure of synuclein-deficient synapses, in short- or long-term synaptic plasticity, or in the pool size or replenishment of recycling synaptic vesicles. However, protein quantitations revealed that KO of synucleins caused selective changes in two small synaptic signaling proteins, complexins and 14-3-3 proteins. Moreover, we found that dopamine levels in the brains of double-KO but not single-KO mice were decreased by ≈20%. In contrast, serotonin levels were unchanged, and dopamine uptake and release from isolated nerve terminals were normal. These results show that synucleins are not essential components of the basic machinery for neurotransmitter release but may contribute to the long-term regulation and/or maintenance of presynaptic function.
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αSyn-KO and α/β-Syn double-KO mice exhibit reduced brain dopamine levels compared to wild-type animals.
“However, αSyn-KO, and α/β-Syn double-KO mice exhibited reduced brain dopamine levels compared to wild-type (wt) animals”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [157]
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- Authors
- Chandra, S., Fornai, F., Kwon, H.-B., Yazdani, U., Atasoy, D., Liu, X., Hammer, R. E., Battaglia, G., German, D. C., Castillo, P. E., & Südhof, T. C.
- Affiliations
- University of Pisa (IT)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-10
- Volume
- 101
- Issue
- 41
- Pages
- 14966-14971
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC522043
- OpenAlex
- W2085082653
- Cited by
- 438
- References
- 40
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 16 · 2023: 14 · 2022: 21 · 2021: 20 · 2020: 14 · 2019: 20 · 2018: 20 · 2017: 14 · 2016: 22 · 2015: 20 · 2014: 25 · 2013: 24 · 2012: 27
- FWCI
- 12.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (1-R01-NS40057, R01NS040057)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- alpha-synuclein, beta-synuclein, double knockout mice, presynaptic function, synaptic plasticity, synaptic vesicle recycling, complexin, 14-3-3 proteins, dopamine levels, neurotransmitter release, Parkinson's disease, synaptic ultrastructure
- MeSH terms
- Animals, Base Sequence, Biological Transport, Corpus Striatum, Dopamine, Electrophysiology, Hippocampus, Nerve Tissue Proteins, Neurons, Synapses, Synaptic Vesicles, DNA Primers, Mice, Knockout, Mice, Synucleins, alpha-Synuclein, beta-Synuclein
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