Donepezil modulates amyloid precursor protein endocytosis and reduction by up-regulation of SNX33 expression in primary cortical neurons.

ABSTRACT: Donepezil, a therapeutic drug for Alzheimer's disease, ameliorates cognitive dysfunction through selective inhibition of acetylcholinesterase. However, recent studies have also reported off-target effects of donepezil that likely contribute to its therapeutic effects. In this study, we investigated the (i) role of donepezil in amyloid precursor protein (APP) processing and (ii) involvement of sorting nexin protein 33 (SNX33), a member of the sorting nexin protein family, in this processing. Results showed that donepezil induces an increase in SNX33 expression in primary cortical neurons. The secretion of sAPPα in culture media increased, whereas the expression of full-length APP in the cell lysate remained unchanged. Exposure of cortical cultures to donepezil led to a decrease in amyloid β

SUBMITTER: Takada-Takatori Y 

PROVIDER: S-EPMC6695423 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature