N-acetyl-L-cysteine protects SHSY5Y neuroblastoma cells from oxidative stress and cell cytotoxicity: effects on beta-amyloid secretion and tau phosphorylation

Redox changes within neurones are increasingly being implicated as an impor tant causative agent in brain ageing and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheime r's disease (AD). cells have developed a number of defensive mechanisms to maintain intracellular redox homeostasis, including the glutathione (GSH) s ystem and antioxidant enzymes. Here we examine the effects of N-acetyl-L-cy steine (NAC) on beta -amyloid (A beta) secretion and tau phosphorylation in SHSY5Y neuroblastoma cells after exposure to oxidative stress inducing/cyt otoxic compounds (H2O2, UV light and toxic A beta peptides). A beta and tau protein are hallmark molecules in the pathology of AD while the stress fac tors are implicated in the aetiology of AD. The results show that H2O2, UV light, A beta1-42 and toxic A beta 25-35, but not the inactive A beta 35-25 , produce a-significant induction of oxidative stress and cell cytotoxicity . The effects are reversed when cells are pre; treated with 30 mM NAC. Cell s exposed to H2O2, UV light and A beta 25-35, but not A beta 35-25, secrete significantly higher amounts of A beta1-40 and A beta1-42 into the culture medium. NAC pre-treatment increased the release of A beta1-40 compared wit h controls and potentiated the release of both A beta1-40 and A beta1-42 in A beta 25-35-treated cells. Tau phosphorylation was markedly reduced by H2 O2 and UV light but increased by A beta 25-35. NAC strongly lowered phospho -tau levels in the presence or absence of stress treatment.