In vivo and in vitro studies on the roles of p38 mitogen-activated protein kinase and NADPH-cytochrome P450 reductase in Alzheimer's disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease with an increasing morbidity rate. As one of the most important signaling pathways that responds to inflammation and degeneration, the p38 mitogen-activated protein kinase (MAPK) signaling pathway is active in the cortexes of AD mice. At the cellular level the same effect can be observed with p38 MAPK when induced by amyloid β (Aβ)1-42 , a 42-residue Aβ fragment. Inhibition of p38 MAPK in the present study protected SH-SY5Y cells from the toxicity of Aβ1-42 , and alleviated the formation of senile plaques and cognitive impairment in AD mice. The expression of cytochrome P450 reductase (CPR) in the brains of mice with AD, in addition to Aβ1-42 -treated SH-SY5Y cells, also increased. However, the inhibition of CPR did not protect SH-SY5Y cells from the toxicity of Aβ1-42 . The results of the present study suggest that p38 MAPK is a potential therapeutic target for the treatment of AD. In addition, the main enzyme that metabolizes drugs, CPR, could serve a more complex role in AD.