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β-Synuclein Inhibits α-Synuclein Aggregation
Open accessAbstract
We characterized beta-synuclein, the non-amyloidogenic homolog of alpha-synuclein, as an inhibitor of aggregation of alpha-synuclein, a molecule implicated in Parkinson's disease. For this, doubly transgenic mice expressing human (h) alpha- and beta-synuclein were generated. In doubly transgenic mice, beta-synuclein ameliorated motor deficits, neurodegenerative alterations, and neuronal alpha-synuclein accumulation seen in halpha-synuclein transgenic mice. Similarly, cell lines transfected with beta-synuclein were resistant to alpha-synuclein accumulation. halpha-synuclein was coimmunoprecipitated with hbeta-synuclein in the brains of doubly transgenic mice and in the double-transfected cell lines. Our results raise the possibility that beta-synuclein might be a natural negative regulator of alpha-synuclein aggregation and that a similar class of endogenous factors might regulate the aggregation state of other molecules involved in neurodegeneration. Such an anti-amyloidogenic property of beta-synuclein might also provide a novel strategy for the treatment of neurodegenerative disorders.
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“-Synuclein inhibits ␣-synuclein aggregation in mice, and mouse tau may retard human tau aggregation (Rochet et al., 2000;Hashimoto et al., 2001;Andorfer et al., 2003).”
From Aβ40 Inhibits Amyloid Deposition In Vivo (2007) · cites this paper as Hashimoto et al., 2001
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Self-citationVekrellis, K., Rideout, H. J., & Stefanis, L. (2004) · Molecular Neurobiology · doi:10.1385/mn:30:1:001 · Cited by 108
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Forcing Nonamyloidogenic β-Synuclein To Fibrillate
Yamin, G., Munishkina, L. A., Karymov, M. A., Lyubchenko, Y. L., Uversky, V. N., & Fink, A. L. (2005) · Biochemistry · doi:10.1021/bi048778a · Cited by 103
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Self-citationRetractedγ‐Synuclein and the progression of cancer
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Parkinson's Disease-associated α-Synuclein Is a Calmodulin Substrate
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Molecular determinants of the aggregation behavior of α‐ and β‐synuclein
Rivers, R. C., Kumita, J. R., Tartaglia, G. G., Dedmon, M. M., Pawar, A. P., Vendruscolo, M., Dobson, C. M., & Christodoulou, J. (2008) · Protein Science · doi:10.1110/ps.073181508 · Cited by 97
Immunological features of α‐synuclein in Parkinson's disease
Roodveldt, C., Christodoulou, J., & Dobson, C. M. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00450.x · Cited by 97
Design of an N-Methylated Peptide Inhibitor of α-Synuclein Aggregation Guided by Solid-State NMR
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Preventing α-synuclein aggregation: The role of the small heat-shock molecular chaperone proteins
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Role of Individual Methionines in the Fibrillation of Methionine-Oxidized α-Synuclein
Hokenson, M. J., Uversky, V. N., Goers, J. W. F., Yamin, G., Munishkina, L. A., & Fink, A. L. (2004) · Biochemistry · doi:10.1021/bi049979h · Cited by 97
Targeted Mass Spectrometry Suggests Beta-Synuclein as Synaptic Blood Marker in Alzheimer’s Disease
Oeckl, P., Halbgebauer, S., Anderl‐Straub, S., Arnim, C. A. F. V., Diehl‐Schmid, J., Froelich, L., Grimmer, T., Hausner, L., Denk, J., Jahn, H., et al. (2020) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00824 · Cited by 93
Metadata
- Authors
- Hashimoto, M., Rockenstein, E., Mante, M., Mallory, M., & Masliah, E.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Masliah, Eliezer
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2001-10
- Volume
- 32
- Issue
- 2
- Pages
- 213-223
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2064132534
- Cited by
- 398
- References
- 60
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 11 · 2023: 7 · 2022: 10 · 2021: 11 · 2020: 14 · 2019: 7 · 2018: 17 · 2017: 10 · 2016: 11 · 2015: 16 · 2014: 17 · 2013: 18 · 2012: 20
- FWCI
- 19.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG10689, R01AG010689, P50AG005131, AG-5131, AG 18440)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- beta-synuclein, alpha-synuclein, protein aggregation, Parkinson's disease, neurodegeneration, transgenic mice, motor impairment, protein-protein interaction, neurodegenerative disease treatment
- MeSH terms
- Animals, Antiparkinson Agents, Brain, Humans, Immunosorbent Techniques, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Motor Activity, Nerve Tissue Proteins, Recombinant Proteins, Transfection, Gene Expression, Dimerization, Neurodegenerative Diseases, Mice, Synucleins, alpha-Synuclein, beta-Synuclein
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