Aggregates from mutant and wild-type alpha-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of beta-sheet and amyloid-like filaments

alpha-Synuclein (alpha-syn) protein and a fragment of it, called NAG, have been found in association with the pathological lesions of a number of neur odegenerative diseases, Recently, mutations in the alpha-syn gene have been reported in families susceptible to an inherited form of Parkinson's disea se. We have shown that human wild-type alpha-syn, mutant alpha-syn(Ala30Pro ) and mutant alpha-syn(Ala53Thr) proteins can self-aggregate and form amylo id-like filaments, Here we report that aggregates of NAC and alpha-syn prot eins induced apoptotic cell death in human neuroblastoma SH-SY5Y cells. The se findings indicate that accumulation of alpha-syn and its degradation pro ducts may play a major role in the development of the pathogenesis of these neurodegenerative diseases. (C) 1998 Federation of European Biochemical So cieties.