Biological Activity
arn2966 is a potent post-transcriptional modulator of amyloid precursor protein (app) expression in transfected cho cells. the cho cell can produce app.[1]app is the amyloid precursor protein of alzheimer’s disease. alzheimer’s disease is a progressive dementia with the symptoms of neuronal degeneration, synaptic loss, and the deposition of amyloid fibrils in the brain. ab protein is the major constituent of the amyloid . then the ab protein derives from the amyloid precursor protein (app). it has been proved that app can stimulate neurite outgrowth in vitro. [2]the modulation of app expression of the arn2966 functions as a post-transcriptional modulation,which is different from other mechanisms such as inhibition of secretases. arn2966 showed dose dependant inhibition of aß40 and aß42 productions in app751sw transfected cho cells (ic50<1 mm for aß40), along with lowering the level of app and c83, and c99 peptides, while the level of app mrna was unaffected..[1]there has been ad transgenic mice model proved arn2966’s efficacy and tolerability in vivo. through the treatment of arn2966, the memory of mice has been improved and a load in the brain has been reduced.
References
[1] ayodeji asuni ,xu kevin , etal. , an app translation modulator arn2966 reduces beta-amyloid deposition and prevents memory deficits in alzheimer's disease transgenic mice. alzheimer's & dementia: the journal of the alzheimer's association, july 2012volume 8, issue 4, supplement, page s744 ;
[2]williamson tg1, mok ss, henry a, etal. , secreted glypican binds to the amyloid precursor protein of alzheimer's disease (app) and inhibits app-induced neurite outgrowth. j biol chem. 1996 dec 6;271(49):31215-21.
