An Overview of β-Amyloid Cleaving Enzyme 1 (BACE1) in Alzheimer's Disease Therapy: Elucidating its Exosite-Binding Antibody and Allosteric Inhibitor

Abstract

Over decades of its identification, numerous past and ongoing research has focused on β- amyloid cleaving enzyme 1 (BACE1) therapeutic roles as a target in treating Alzheimer's disease (AD). Although the initial BACE1 inhibitors at phase-3 clinical trials tremendously reduced β -amyloidassociated plaques in patients with AD, the researchers eventually discontinued the tests for lack of potency. This discontinuation has resulted in limited drug development and discovery targeted at BACE1, despite the high demand for dementia and AD therapies. It is, therefore, imperative to describe the detailed underlying biological basis of the BACE1 therapeutic option in neurological diseases. Herein, we highlight BACE1 bioactivity, genetic properties, and role in neurodegenerative therapy. We review research contributions on BACE1 exosite-binding antibody and allosteric inhibitor development as AD therapies. The review also covers BACE1 biological function, the disease-associated mechanisms, and the enzyme conditions for amyloid precursor protein site splitting. Based on the present review, we suggest further studies on anti-BACE1 exosite antibodies and BACE1 allosteric inhibitors. Non-active site inhibition might be the way forward to BACE1 therapy in Alzheimer's neurological disorder.

Keywords: Allosteric inhibitors.; Alzheimer's disease; BACE1 biological properties; BACE1 exosites antibody; BACE1 substrates; Gene expression.