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.