Parkinson's disease and related alpha-synucleinopathies are brain amyloidoses.
A paradigm shift in understanding Parkinson's disease (PD) and related disorders is emerging from studies showing that alpha-synuclein (AS) gene mutations cause familial PD; AS is abnormally nitrated, phosphorylated, and ubiquitinated; AS forms neuronal and glial inclusions; AS fibrillizes in vitro; and AS transgenic animals develop neurodegeneration with AS amyloid inclusions. Thus, PD and related synucleinopathies are brain amyloidoses that may share similar mechanisms and targets for drug discovery.
Trojanowski
John Q
JQ
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. trojanow@mail.med.upenn.edu
Lee
Virginia M-Y
VM
D000686:Amyloidosis / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein