Publication Date:
2000-11-04
Description:
Aggregated alpha-synuclein proteins form brain lesions that are hallmarks of neurodegenerative synucleinopathies, and oxidative stress has been implicated in the pathogenesis of some of these disorders. Using antibodies to specific nitrated tyrosine residues in alpha-synuclein, we demonstrate extensive and widespread accumulations of nitrated alpha-synuclein in the signature inclusions of Parkinson's disease, dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and multiple system atrophy brains. We also show that nitrated alpha-synuclein is present in the major filamentous building blocks of these inclusions, as well as in the insoluble fractions of affected brain regions of synucleinopathies. The selective and specific nitration of alpha-synuclein in these disorders provides evidence to directly link oxidative and nitrative damage to the onset and progression of neurodegenerative synucleinopathies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Giasson, B I -- Duda, J E -- Murray, I V -- Chen, Q -- Souza, J M -- Hurtig, H I -- Ischiropoulos, H -- Trojanowski, J Q -- Lee, V M -- New York, N.Y. -- Science. 2000 Nov 3;290(5493):985-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurodegenerative Disease Research and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11062131" target="_blank"〉PubMed〈/a〉
Keywords:
Alzheimer Disease/metabolism/pathology
;
Antibodies, Monoclonal
;
Blotting, Western
;
Brain/*metabolism/pathology
;
Brain Chemistry
;
Enzyme-Linked Immunosorbent Assay
;
Fluorescent Antibody Technique
;
Humans
;
Immunohistochemistry
;
Lewy Bodies/chemistry
;
Lewy Body Disease/metabolism/pathology
;
Microscopy, Immunoelectron
;
Multiple System Atrophy/metabolism/pathology
;
Nerve Tissue Proteins/analysis/immunology/*metabolism
;
Neurodegenerative Diseases/*metabolism/*pathology
;
Neurons/chemistry/metabolism/ultrastructure
;
*Oxidative Stress
;
Parkinson Disease/metabolism/pathology
;
Synucleins
;
Tyrosine/*analogs & derivatives/analysis/immunology/*metabolism
;
alpha-Synuclein
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
