BACE1 inhibitors: A promising therapeutic approach for the management of Alzheimer’s disease

Abstract

Alzheimer’s disease is a neurological disorder marked by the accumulation of amyloid beta (Aβ) aggregates, resulting from mutations in the amyloid precursor protein. The enzyme β-secretase, also known as β-site amyloid precursor protein cleaving enzyme 1 (BACE1), plays a crucial role in generating Aβ peptides. With no targeted therapy available for Alzheimer’s disease, inhibiting BACE1 aspartic protease has emerged as a primary treatment target. Since 1999, compounds demonstrating potential binding to the BACE1 receptor have advanced to human trials. Structural optimization of synthetically derived compounds, coupled with computational approaches, has offered valuable insights for developing highly selective leads with drug-like properties. This review highlights pivotal studies on the design and development of BACE1 inhibitors as anti-Alzheimer’s disease agents. It summarizes computational methods employed in facilitating drug discovery for potential BACE1 inhibitors and provides an update on their clinical status, indicating future directions for novel BACE1 inhibitors. The promising clinical results of Elenbecestat (E-2609) catalyze the development of effective, selective BACE1 inhibitors in the future.