A close association of torsinA and alpha-synuclein in Lewy bodies: a fluorescence resonance energy transfer study.
TorsinA, a novel protein in which a mutation causes dominant, early onset torsion dystonia, may serve as a chaperone for misfolded proteins that require refolding or degradation. It has been hypothesized that misfolded alpha-synuclein, a protein in which two mutations cause autosomal dominantly inherited Parkinson's disease, serves as a nidus for the development of a Lewy body. We hypothesized that torsinA plays a role in the cellular processing of alpha-synuclein. We demonstrate that anti-torsin antibodies stain Lewy bodies and Lewy neurites in the substantia nigra and cortex. Using sensitive fluorescent resonance energy transfer (FRET) techniques, we find evidence of a close association between torsinA and alpha-synuclein in Lewy bodies.
Sharma
N
N
Department of Neurology, Alzheimer's Disease Research Unit, and the Department of Neurology, Molecular Neurogenetics Unit, Massachusetts General Hospital East, Charlestown, Massachusetts. Albert Einstein College of Medicine, Bronx, New York.
Hewett
J
J
Ozelius
L J
LJ
Ramesh
V
V
McLean
P J
PJ
Breakefield
X O
XO
Hyman
B T
BT
D002352:Carrier Proteins; D004735:Energy Transfer; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism*; D020961:Lewy Body Disease / Q000378:metabolism; D018613:Microscopy, Confocal; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012016:Reference Values; D013050:Spectrometry, Fluorescence; D013378:Substantia Nigra / Q000378:metabolism*; D051843:Synucleins; D051844:alpha-Synuclein
D002352:Carrier Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; C108175:TOR1A protein, human; D051844:alpha-Synuclein