References
Query Results -- Details
MGI Accession ID: MGI:3774266
J Number: J:131733
Other Accession IDs:
Title: A molecular pathway of neurodegeneration linking alpha-synuclein to ApoE and Abeta peptides.
Authors: Gallardo G; Schluter OM; Sudhof TC
Journal: Nat Neurosci
Volume: 11
Issue: 3
Date: 2008 Mar
Year: 2008
Pages: 301-8
Review Status: Peer Reviewed
Abstract:
Pathogenic aggregates of alpha-synuclein are thought to contribute to the development of Parkinson's disease. Inclusion bodies containing alpha-synuclein are present in Parkinson's disease and other neurodegenerative diseases, including Alzheimer's disease. Moreover, alpha-synuclein mutations are found in cases of familial Parkinson's disease, and transgenic overexpression of alpha-synuclein causes neurodegeneration in mice. The molecular mechanisms involved, however, remain incompletely understood. Here we show that, in transgenic mice, alpha-synuclein induced neurodegeneration involves activation of the ubiquitin/proteasome system, a massive increase in apolipoprotein E (ApoE) levels and accumulation of insoluble mouse Abeta. ApoE was not protective, but was injurious, as deletion of ApoE delayed the neurodegeneration caused by alpha-synuclein and suppressed the accumulation of Abeta. Our data reveal a molecular link between central pathogenic mechanisms implicated in Parkinson's disease and Alzheimer's disease and suggest that intracellular alpha-synuclein is pathogenic, at least in part, by activation of extracellular signaling pathways involving ApoE.
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