Differences between normal and alpha-synuclein overexpressing SH-SY5Y neuroblastoma cells after Aβ(1-42) and NAC treatment

Abstract Alpha-synuclein (αSN) plays a major role in numerous neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Intracellular inclusions containing aggregated αSN have been reported in Alzheimer's and Parkinson's affected brains. Moreover, a proteolytic fragment of αSN, the so-called non-amyloid component of Alzheimer's disease amyloid (NAC) was found to be an integral part of Alzheimer's dementia related plaques. Despite the extensive research on this topic, the exact toxic mechanism of αSN remains elusive. We have taken the advantage of an αSN overexpressing SH-SY5Y cell line and investigated the effects of classical apoptotic factors (e.g. H 2 O 2 , amphotericin B and ruthenium red) and aggregated disease-related peptides on cell viability compared to wild type neuroblastoma cells. It was found that αSN overexpressing cells are more sensitive to aggregated peptides treatment than normal expressing counterparts. In contrast, cells containing elevated amount of αSN were less vulnerable to classical apoptotic stressors than wild type cells. In addition, αSN overexpression is accompanied by altered phenotype, attenuated proliferation kinetics, increased neurite arborisation and decreased cell motility. Based on these results, the αSN overexpressing cell lines may represent a good and effective in vitro model for Alzheimer's and Parkinson's disease.