Dual Inhibitors of AChE and BACE-1 for Reducing Aβ in Alzheimer's Disease: From In Silico to In Vivo.

ABSTRACT: Alzheimer's disease (AD) is a complex and widespread condition, still not fully understood and with no cure yet. Amyloid beta (Aβ) peptide is suspected to be a major cause of AD, and therefore, simultaneously blocking its formation and aggregation by inhibition of the enzymes BACE-1 (β-secretase) and AChE (acetylcholinesterase) by a single inhibitor may be an effective therapeutic approach, as compared to blocking one of these targets or by combining two drugs, one for each of these targets. We used our ISE algorithm to model each of the AChE peripheral site inhibitors and BACE-1 inhibitors, on the basis of published data, and constructed classification models for each. Subsequently, we screened large molecular databases with both models. Top scored molecules were docked into AChE and BACE

SUBMITTER: Stern N 

PROVIDER: S-EPMC9655245 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature