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
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.