BACE1: A Key Regulator in Alzheimer's Disease Progression and Current Development of its Inhibitors

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease with no specific disease-modifying treatment. beta-secretase (BACE1) is considered the potential and rationale target because it is involved in the rate-limiting step, which produces toxic A beta(42) peptides that leads to deposits in the form of amyloid plaques extracellularly, resulting in AD. Objective: This study aims to discuss the role and implications of BACE1 and its inhibitors in the management of AD. Methods: We have searched and collected the relevant quality work from PubMed using the following keywords BACE1, BACE2, inhibitors, and Alzheimer's disease. In addition, we included the work which discusses the role of BACE1 in AD and the recent work on its inhibitors. Results: In this review, we have discussed the importance of BACE1 in regulating AD progression and the current development of BACE1 inhibitors. However, the development of a BACE1 inhibitor is very challenging due to the large active site of BACE1. Nevertheless, some of the BACE1 inhibitors have managed to enter advanced phases of clinical trials, such as MK-8931 (Verubecestat), E2609 (Elenbecestat), AZD3293 (Lanabecestat), and JNJ-54861911 (Atabecestat). This review also sheds light on the prospect of BACE1 inhibitors as the most effective therapeutic approach in delaying or preventing AD progression. Conclusion: BACE1 is involved in the progression of AD. The current ongoing or failed clinical trials may help understand the role of BACE1 inhibition in regulating the A beta load and cognitive status of AD patients.

Automated summary

This article discusses the importance of BACE1 in regulating the progression of Alzheimer's disease (AD) and the development of BACE1 inhibitors. Despite the challenges involved in developing BACE1 inhibitors, some inhibitors have reached advanced stages of clinical trials. BACE1 inhibitors have the potential to be the most effective therapeutic approach in delaying or preventing AD progression.