Thursday, December 6, 2012
Figure 1. APP processing in AD. In early Alzheimer's disease
pathogenesis, amyloid precursor protein
(APP) is processed by a
series of proteases to yield several neurotoxic protein fragments. First, APP
is cut by b-site APP-cleaving enzyme 1
(BACE1) [a] to yield a fragment
called C99 [b], which is subsequently cut by the g-secretase complex [c] to yield b-amyloid (Ab).
et al. have provided in vivo evidence in a mouse model of AD that
suggests intracellular C99 accumulation contributes to early AD pathology.
Thathiah et al. have shown that arrestin b2 (ARRB2) acts as a g-secretase cofactor that specifically
regulates the processing of C99.