Protective effects of BACE1 inhibitory ligand molecules against amyloid beta-induced synaptic and mitochondrial toxicities in Alzheimer's disease.

ABSTRACT: Amyloid-β (Aβ) peptides are the major drivers of Alzheimer's disease (AD) pathogenesis, and are formed by successive cleavage of the amyloid precursor protein (APP) by the beta and gamma secretases. Mounting evidence suggests that Aβ and mitochondrial structural and functional abnormalities are critically involved in the loss of synapses and cognitive decline, in patients with AD. In AD brain, state the sequential proteolytic cleavage of APP by beta secretase 1 enzyme (BACE1) and γ-secretase leads to the production and release of Aβ40 and 42. BACE1 expression and activity increased in the brains of AD patients. Structurally, β-secretase has a very large binding site (1000 Å) with fewer hydrophobic domains that makes a challenge to identify the specific targets/binding sites of BACE1. In th

SUBMITTER: Pradeepkiran JA 

PROVIDER: S-EPMC7001603 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature