ARN2966

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Background

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.

[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.