The experimental Alzheimer's disease drug posiphen [-phenserine] lowers amyloid-beta peptide levels in cell culture and mice

J Pharmacol Exp Ther 320:386-96 (2007)
  Copy   BIBTEX

Abstract

Major characteristics of Alzheimer's disease are synaptic loss, cholinergic dysfunction, and abnormal protein depositions in the brain. The amyloid beta-peptide , a proteolytic fragment of amyloid beta precursor protein , aggregates to form neuritic plaques and has a causative role in AD. A present focus of AD research is to develop safe Abeta-lowering drugs. A selective acetylcholinesterase inhibitor, phenserine, in current human trials lowers both APP and Abeta. Phenserine is dose-limited in animals by its cholinergic actions; its cholinergically inactive enantiomer, posiphen -[phenserine], was assessed. In cultured human neuroblastoma cells, posiphen, like phenserine, dose- and time-dependently lowered APP and Abeta levels by reducing the APP synthesis rate. This action translated to an in vivo system. Posiphen administration to mice significantly decreased levels of total APP in a dose-dependent manner. Abeta40 and Abeta42 levels were significantly lowered by posiphen compared with controls. The activities of alpha-, beta-, and gamma-secretases were assessed in the same brain samples, and beta-secretase activity was significantly reduced. Posiphen, like phenserine, can lower Abeta via multiple mechanisms and represents an interesting drug candidate for AD treatment

Links

PhilArchive



    Upload a copy of this work     Papers currently archived: 94,385

External links

Setup an account with your affiliations in order to access resources via your University's proxy server

Through your library

Similar books and articles

Analytics

Added to PP
2015-06-29

Downloads
20 (#771,272)

6 months
4 (#1,037,980)

Historical graph of downloads
How can I increase my downloads?

Author Profiles

Tonimarie Giordano
Kean College of New Jersey
Qing Yu
Royal Holloway University of London
Bryan Maloney
Indiana University Purdue University, Indianapolis

Citations of this work

No citations found.

Add more citations

References found in this work

No references found.

Add more references