-Synuclein in Parkinson's Disease
Open accessAbstract
α-Synuclein is a presynaptic neuronal protein that is linked genetically and neuropathologically to Parkinson's disease (PD). α-Synuclein may contribute to PD pathogenesis in a number of ways, but it is generally thought that its aberrant soluble oligomeric conformations, termed protofibrils, are the toxic species that mediate disruption of cellular homeostasis and neuronal death, through effects on various intracellular targets, including synaptic function. Furthermore, secreted α-synuclein may exert deleterious effects on neighboring cells, including seeding of aggregation, thus possibly contributing to disease propagation. Although the extent to which α-synuclein is involved in all cases of PD is not clear, targeting the toxic functions conferred by this protein when it is dysregulated may lead to novel therapeutic strategies not only in PD, but also in other neurodegenerative conditions, termed synucleinopathies.
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Genes driving these enrichments included SCNA for the tau pathway; apolipoprotein genes (APOM, APOA5) and ABCA1 for the lipid metabolism pathways; and 52 immune pathway genes.
“Genes driving these enrichments (that is, having a gene-wide P < 0.05) included SCNA, a Parkinson’s risk gene that encodes alpha-synuclein, the main component of Lewy bodies, whch may play a role in tauopathies62,63, for the tau pathway; apolipoprotein genes (APOM, APOA5) and ABCA1, a major regulator of cellular cholesterol, for the lipid metabolism pathways; and 52 immune pathway genes”
From Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (2019) · cites this paper as [62]
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Cell-produced α-synuclein oligomers are targeted to, and impair, the 26S proteasome
Emmanouilidou, E., Stefanis, L., & Vekrellis, K. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.07.008 · Cited by 221 · see citing works
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Magnesium Inhibits Spontaneous and Iron-induced Aggregation of α-Synuclein
Golts, N., Snyder, H. M., Frasier, M. A., Theisler, C. M., Choi, P., & Wolozin, B. L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107866200 · Cited by 215 · see citing works
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Demonstration of a role for α-synuclein as a functional microtubule-associated protein
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Tubulin Seeds α-Synuclein Fibril Formation
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Genetic Variants of the α-Synuclein Gene SNCA Are Associated with Multiple System Atrophy
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Effect of 4-Hydroxy-2-nonenal Modification on α-Synuclein Aggregation
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- Authors
- Stefanis, L.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- Corresponding author
- Stefanis, L.
- ORCID
- Stefanis, L.
- Venue
- Cold Spring Harbor Perspectives in Medicine
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-12-13
- Volume
- 2
- Issue
- 2
- Pages
- a009399-a009399
- ISSN
- 2157-1422 (ISSN-L)
- PMC
- PMC3281589
- OpenAlex
- W2117503265
- Cited by
- 1,446
- References
- 292
- Citations by year
- 2026: 100 · 2025: 180 · 2024: 226 · 2023: 149 · 2022: 166 · 2021: 154 · 2020: 117 · 2019: 72 · 2018: 68 · 2017: 60 · 2016: 51 · 2015: 48 · 2014: 34 · 2013: 18 · 2012: 3
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- alpha-synuclein, Parkinson's disease, protofibrils, protein aggregation, synaptic dysfunction, neuronal cell death, disease propagation, synucleinopathies, neurodegeneration, therapeutic target
- MeSH terms
- Animals, Cell Nucleus, Cytoskeleton, Disease Models, Animal, Endoplasmic Reticulum, Golgi Apparatus, Humans, Mitochondria, Parkinson Disease, Biomarkers, Oxidative Stress, Protein Modification, Translational, alpha-Synuclein, Proteolysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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