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Oxidative Damage Linked to Neurodegeneration by Selective -Synuclein Nitration in Synucleinopathy Lesions
Benoit I. Giasson,1*John E. Duda,1*Ian V. J. Murray,1Qiping Chen,3José M. Souza,3Howard I. Hurtig,2Harry Ischiropoulos,3John Q. Trojanowski,1Virginia
M. -Y. Lee1
Aggregated -synuclein proteins form brain lesions that are
hallmarks of neurodegenerative synucleinopathies, and oxidativestress
has been implicated in the pathogenesis of some of thesedisorders.
Using antibodies to specific nitrated tyrosine residuesin
-synuclein, we demonstrate extensive and widespread accumulationsof
nitrated -synuclein in the signature inclusions of Parkinson'sdisease, dementia with Lewy bodies, the Lewy body variant of
Alzheimer'sdisease, and multiple system atrophy brains. We also show
thatnitrated -synuclein is present in the major filamentous
buildingblocks of these inclusions, as well as in the insoluble
fractionsof affected brain regions of synucleinopathies. The selectiveand specific nitration of -synuclein in these disorders providesevidence to directly link oxidative and nitrative damage to theonset
and progression of neurodegenerative synucleinopathies.
1 Center for Neurodegenerative Disease Research
and Department of Pathology and Laboratory Medicine,
2 Department of Neurology, University of
Pennsylvania, Philadelphia, PA 19104, USA.
3 Stokes
Research Institute and Department of Biochemistry and Biophysics,
Children's Hospital of Philadelphia and University of Pennsylvania,
Philadelphia, PA 19104, USA.
*
These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail:
vmylee{at}mail.med.upenn.edu
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In Science Magazine
LETTERS
George Perry, Jesús Avila, Michael G. Espey, David A. Wink, Craig S. Atwood, Mark A. Smith;, Harry Ishiropoulos, Benoit Giasson, John E. Duda, John Q. Trojanowski, and Virginia M.-Y. Lee (26 January 2001) Science291 (5504), 595c.
[DOI: 10.1126/science.291.5504.595C] |Full Text »
-Synuclein Nitration in Synucleinopathy Lesions
-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
