Critical analysis of the use of β-site amyloid precursor protein-cleaving enzyme 1 inhibitors in the treatment of Alzheimer's disease

摘要: Alzheimer's disease (AD) is the major cause of dementia in elderly and an unmet clinical challenge. A variety therapies that are currently under development directed to amyloid cascade. Indeed, accumulation toxicity amyloid-β (Aβ) believed play a central role etiology disease, thus rational interventions aimed at reducing levels Aβ brain. Targeting β-site precursor protein-cleaving enzyme (BACE)-1 represents attractive strategy, as this catalyzes initial rate-limiting step production. Observation increased BACE1 enzymatic activity brain, cerebrospinal fluid, platelets patients with AD mild cognitive impairment supports potential benefits inhibition. Numerous potent inhibitors have been generated, many these proved lower brain animal models. Over 10 years intensive research on has now culminated advancing half dozen drugs into human trials, yet translating vitro cellular efficacy preclinical trials This review addresses promises also problems associated for therapy, complex biological function becoming unraveled.