Effects of rivastigmine on secreted amyloid precursor protein and beta-amyloid secretion in neuroblastoma SK-N-SH cells

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized clinically by progressive impairment of memory and cognition. The currently available pharmacological treatment of AD consists mainly of cholinesterase inhibitors. Rivastigmine is one of the cholinesterase inhibitors clinically used to treat this disease, and many clinical trials have indicated that it did alleviate some AD symptoms without causing apparent side effects. Since the amyloid precursor protein (APP) processing imbalance plays a crucial role in AD pathogenesis, the effects of rivastigmine on APP processing were investigated. In neuroblastoma SK-N-SH cells, rivastigmine significantly increased the secretion of sAPPα and decreased the release of Aβ40 and Aβ42 as compared with control group, but it has no effect on cellular full length APP expression. Rivastigmine significantly increased α-secretase activity and decreased β-secretase activity as compared with control group. The increased sAPPα can be partially blocked by muscarinic receptor inhibitor scopolamine but not by nicotinic receptor antagonist α-Bungarotoxin. The effect of rivastigmine on sAPPα can be partially reversed by PKC inhibitor GF109203X, ERK inhibitor PD98059 and JNK inhibitor SP600125. The data present here indicated that rivastigmine can regulate APP processing in vitro by increasing sAPPα secretion and decreasing Aβ release and this pharmacological property may underlie the clinical effect of the drug in the treatment of AD patients.