The involvement of mitogen‐activated protein (MAP) kinase in the regulation of amyloid precursor protein processing by novel cholinesterase inhibitors derived from rasagiline

摘要: SPECIFIC AIMSCholinesterase (ChE) inhibitors and selective monoamine oxidase-B (MAO-B) have been reported to beneficial effects in Alzheimer’s disease (AD) patients. We recently developed a series of novel bifunctional anti-AD drugs—TV3326 [(N-propargyl-(3R)-aminoindan-5-yl)-ethyl methyl carbamate] its S-isomer TV3279–in an attempt combine the pharmacophore neuroprotective properties anti-Parkinson’s MAO-B inhibitor drug rasagiline (N-propargyl-(1R)-aminoindan) with ChE inhibitory moiety rivastigmine, proven efficacy AD. TV3326 possesses MAO activities, whereas TV3279, which also inhibits ChE, lacks activity. Similar other inhibitors, both drugs antagonized impairment reference working memory induced by scopolamine, procedure for evaluating drugs. studied these compounds on regulation APP processing, using human SH-SY5Y neuroblastoma rat PC12 cells, rol...