title: PMS777, a new cholinesterase inhibitor with anti-platelet activated factor activity, regulates amyloid precursor protein processing in vitro.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by progressive impairment of memory and cognition. Previous data have shown that beta-amyloid (Abeta) cascade plays a central role in AD pathophysiology and thus drugs regulate amyloid precursor protein (APP) metabolism may have therapeutic potential. Here the effects of PMS777, a new cholinesterase inhibitor with anti-platelet activated factor activity, on APP processing were investigated. Using SH-SY5Y(APP695) cells, it showed that PMS777 treatment caused significant decreased secretion of sAPPalpha into the conditioned media without affecting cellular holoAPP synthesis. When PC12 cells were incubated with PMS777, the same effect was observed. The data also indicated that 10 muM PMS777 incubation decreased the release of Abeta42 into the cell media as compared with vehicle group in SH-SY5Y(APP695) cells. Pretreatment of cells with M-receptor scopolamine antagonized the decreased secretion of sAPPalpha induced by PMS777, but N-receptor alpha-bungarotoxin pretreatment did not have such an effect. These results indicated that PMS777 could modulate APP processing in vitro and that decreasing Abeta generation might demonstrate its therapeutic potential in AD.
authors.affiliation: Department of Neurology, Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Hong-Qi
authors.initials: HQ
authors.lastname: Yang
authors.forename: Zhi-Kun
authors.initials: ZK
authors.lastname: Sun
authors.forename: Yan-Xin
authors.initials: YX
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Mao-Wen
authors.initials: MW
authors.lastname: Ba
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Lu
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Ding
authors.forename: Hong-Zhuan
authors.initials: HZ
authors.lastname: Chen
authors.forename: Sheng-Di
authors.initials: SD
authors.lastname: Chen