The β-secretase enzyme BACE1: A biochemical enigma for Alzheimer's disease.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS(2020)
摘要
Beta site amyloid precursor protein cleaving enzyme 1 (BACE1) is a rational target in Alzheimer's Disease (AD) drug development due to its role in amyloidogenic cleavage of Amyloid Precursor Protein (APP) in generating Amyloid beta (A beta). This beta-secretase cleaves not only Amyloid Precursor Protein (APP) and its homologues, but also small series of substrates including neuregulin and li subunit of voltage-gated sodium channel that play a very important role in the development and normal function of the brain. Moreover, BACE1 is modulated at the post-translational level by several factors that are associated with both physiological and pathological functions. Since the discovery of BACE1 over a decade ago, medicinal chemistry and pharmacokinetics of BACE1 small molecule inhibitors have proven challenging for the treatment of Alzheimer's disease.
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关键词
Alzheimer's disease,Amyloid Precursor Protein (APP),BACE1,Amyloid beta (A beta),beta-pathway,palmitoylation
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