Recent insight into BACE1 as a potential target for treatment of Alzheimer's disease

Document Type : Original Article

Authors

1 Pharmaceutical Chemistry Department, Faculty of Pharmacy, Badr University

2 Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal Uniersity

3 Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University

4 Medicinal Chemistry department , Faculty of Pharmacy,Suez Canal University

5 Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Giza, Egypt

Abstract

Alzheimer’s disease (AD) is one of the most common progressive neurodegenerative diseases that represents about 60-80 % of total cases of dementia all over the world. Beta secretase (BACE1) is a membrane-anchored aspartic protease which cleaves the peptide bond between Met671-Asp672 of APP (amyloid precursor protein) where its activity is the rate limiting step of producing amyloid β, the primary neuropathological hallmark of Alzheimer's disease (AD). Therefore, inhibitors of this enzyme have the potential to be a promising and attractive target for intervention of potent therapeutics for treatment AD. Actually, there are many challenges facing the development of effective drug-like BACE1 inhibitors including penetration of BBB and selectivity against other proteases. However, many efforts have been devoted by pharmaceutical industries and academia for development of small size, potent, selective and biologically active BACE1 inhibitors. Till now, none of which is FDA approved but some of which have exhibited clinical potential. In this article, we outlined overview of beta secretase inhibitors that have been designed and developed for treatment of AD.

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