Molecular pathogenesis of movement disorders: are protein aggregates a common link in neuronal degeneration?

Abnormal protein aggregation has been postulated to explain the molecular b asis for many neurodegenerative diseases, including Alzheimer's disease, Pa rkinson's disease and prion diseases, as well as trinucleotide repeat disor ders. The recent findings that mutations in alpha-synuclein lead to autosom al-dominant, early-onset Parkinson's disease in some families and that alph a-synuclein is found in Lewy bodies of all Parkinson's disease patients pro mpted the hypothesis that the pathophysiology of all Parkinson's disease pa tients starts with an abnormal folding of alpha-synuclein, producing excess ive aggregation that overwhelms the antiaggregation mechanisms of the cell. The genetics of Parkinson's disease and polyglutamine repeat disorders and the evidence of abnormal processing and aggregation of the respective targ et proteins for the aetiology and pathogenesis in these diseases are review ed. Curr Opin Neurol 12:433-439, (C) 1999 Lippincott Williams & Wilkins.