ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Redox changes within neurones are increasingly being implicated as an important causative agent in brain ageing and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD). Cells have developed a number of defensive mechanisms to maintain intracellular redox homeostasis, including the glutathione (GSH) system and antioxidant enzymes. Here we examine the effects of N-acetyl-l-cysteine (NAC) on β-amyloid (Aβ) secretion and tau phosphorylation in SHSY5Y neuroblastoma cells after exposure to oxidative stress inducing/cytotoxic compounds (H2O2, UV light and toxic Aβ peptides). Aβ and tau protein are hallmark molecules in the pathology of AD while the stress factors are implicated in the aetiology of AD. The results show that H2O2, UV light, Aβ1–42 and toxic Aβ25–35, but not the inactive Aβ35–25, produce a significant induction of oxidative stress and cell cytotoxicity. The effects are reversed when cells are pre-treated with 30 mm NAC. Cells exposed to H2O2, UV light and Aβ25–35, but not Aβ35–25, secrete significantly higher amounts of Aβ1–40 and Aβ1–42 into the culture medium. NAC pre-treatment increased the release of Aβ1–40 compared with controls and potentiated the release of both Aβ1–40 and Aβ1–42 in Aβ25–35-treated cells. Tau phosphorylation was markedly reduced by H2O2 and UV light but increased by Aβ25–35. NAC strongly lowered phospho-tau levels in the presence or absence of stress treatment.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.2001.00090.x
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