Regulation of β cleavage of amyloid precursor protein.

Alzheimer's disease ranks the first cause for senile dementia. The amyloid cascade is proposed to contribute to the pathogenesis of this disease. In this cascade, amyloid β peptide (Aβ) is produced through a sequential cleavage of amyloid precursor protein (APP) by β and γ secretases, while its cleavage by α secretase precludes Aβ production and generates neurotrophic sAPPα. Thus, enhancing α secretase activity or suppressing β and γ cleavage may reduce Aβ formation and ameliorate the pathological process of the disease. Several regulatory mechanisms of APP cleavage have been established. The present review mainly summarizes the signaling pathways pertinent to the regulation of APP β cleavage.