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

Abstract

α‐Synuclein (α‐syn) protein and a fragment of it, called NAC, have been found in association with the pathological lesions of a number of neurodegenerative diseases. Recently, mutations in the α‐syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We have shown that human wild‐type α‐syn, mutant α‐syn(Ala30Pro) and mutant α‐syn(Ala53Thr) proteins can self‐aggregate and form amyloid‐like filaments. Here we report that aggregates of NAC and α‐syn proteins induced apoptotic cell death in human neuroblastoma SH‐SY5Y cells. These findings indicate that accumulation of α‐syn and its degradation products may play a major role in the development of the pathogenesis of these neurodegenerative diseases.