Cited by 1,446Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingAlzheimer's disease research and treatments

-Synuclein in Parkinson's Disease

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Stefanis, L.·2012·Cold Spring Harbor Perspectives in Medicine

Abstract

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”

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Authors
Stefanis, L.
Affiliations
National and Kapodistrian University of Athens (GR)
Corresponding author
Stefanis, L.
Venue
Cold Spring Harbor Perspectives in Medicine
Published
2011-12-13
Volume
2
Issue
2
Pages
a009399-a009399
ISSN
2157-1422 (ISSN-L)
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
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

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