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PMID: 10517509 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review

Alpha-synuclein in Lewy body disease and Alzheimer's disease.

Brain pathology (Zurich, Switzerland) ·Vol. 9 ·No. 4 ·1999-10-00 ·Pages 707-20

Hashimoto M, Masliah E

Abstract

Alzheimer's disease (AD) and Lewy body disease (LBD) are the most common causes of dementia in the elderly population. Previous studies have shown that cognitive alterations in these disorders are associated with synaptic loss. Injury and loss of synapses might be associated with altered function of synaptic proteins. Among them, recent studies have shown that abnormal aggregation and accumulation of synaptic proteins, such as alpha-synuclein, might be associated with plaque formation in AD and Lewy body formation in LBD. Further reinforcing the hypothesis that alpha-synuclein plays a major role in the pathogenesis of these disorders, recent work has shown that mutations that alter the conformation of this molecule are associated with familial forms of Parkinson's disease. The mechanisms by which altered function or aggregation of alpha-synuclein might lead to neurodegeneration are not completely clear; however, new evidence points to a potential role for this molecule in synaptic damage and neurotoxicity via amyloid-like fibril formation and mitochondrial dysfunction. In this manuscript we review the data linking alpha-synuclein to the pathogenesis of AD and LBD.

MeSH Terms
Alzheimer Disease/pathology Humans Lewy Body Disease/pathology Nerve Tissue Proteins/metabolism Synucleins alpha-Synuclein
Chemicals
Nerve Tissue Proteins SNCA protein, human Synucleins alpha-Synuclein
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hashimoto M
Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla 92093-0624, USA.
Masliah E
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Article Info
Journal
Brain pathology (Zurich, Switzerland)
Abbr.
Brain Pathol
ISSN
1015-6305
DOI
10.1111/j.1750-3639.1999.tb00552.x
Published
1999-10-00
Pages
707-20
Language
English
Region
Switzerland
NLM ID
9216781
PMCID
PMC8098211
Subset
IM
Grants
NIA NIH HHS · AG10869 · United States
NIA NIH HHS · AG5131 · United States
External Links
PubMed source DOI: 10.1111/j.1750-3639.1999.tb00552.x PMC Full Text View journal details
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