The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Intravesicular Localization and Exocytosis of α-Synuclein and its Aggregates
Open accessAbstract
α-Synuclein (α-syn), particularly in its aggregated forms, is implicated in the pathogenesis of Parkinson's disease and other related neurological disorders. However, the normal biology of α-syn and how it relates to the aggregation of the protein are not clearly understood. Because of the lack of the signal sequence and its predominant localization in the cytosol, α-syn is generally considered exclusively an intracellular protein. Contrary to this assumption, here, we show that a small percentage of newly synthesized α-syn is rapidly secreted from cells via unconventional, endoplasmic reticulum/Golgi-independent exocytosis. Consistent with this finding, we also demonstrate that a portion of cellular α-syn is present in the lumen of vesicles. Importantly, the intravesicular α-syn is more prone to aggregation than the cytosolic protein, and aggregated forms of α-syn are also secreted from cells. Furthermore, secretion of both monomeric and aggregated α-syn is elevated in response to proteasomal and mitochondrial dysfunction, cellular defects that are associated with Parkinson's pathogenesis. Thus, intravesicular localization and secretion are part of normal life cycle of α-syn and might also contribute to pathological function of this protein.
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Cites
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
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Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein
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Self-citation-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446
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“Indeed, part of intracellular -synuclein was found previously to be localized in secretory vesicles (Lee et al., 2005).”
BackgroundInfluentialCompromised MAPK signaling in human diseases: an update
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Metadata
- Authors
- Lee, H.-J., Patel, S., & Lee, S.-J.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-06-22
- Volume
- 25
- Issue
- 25
- Pages
- 6016-6024
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2089900719
- Cited by
- 797
- References
- 11
- FWCI
- 8.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
