Guanidine-based ? amyloid precursor protein cleavage enzyme 1 (BACE-1) inhibitors for the Alzheimer?s disease (AD): A review

Alzheimer's disease (AD) is an irreversible, progressive neurological disorder characterized by amyloid plaques, hyperphosphorylated tau protein (hyper p-tau), neuronal damage, memory loss, etc. Various factors, such as age, lifestyle, family history, environmental factors, and gene mutation, cause AD. BACE-1 is an interesting target to prevent or reverse AD progression. BACE-1 cleaves amyloid precursor protein (APP) into soluble amyloid pre-cursor protein beta (sAPP beta) and membrane-bound C-terminal fragment called C99, a rate-limiting step, and C99 is further cleaved by gamma-secretase to generate neurotoxic amyloid beta (A beta). Discovery and development of se-lective beta amyloid precursor protein cleavage enzyme 1 (BACE-1) inhibitors have a great potential for the treatment and maintenance of Alzheimer's disease. In this review, we have compiled literature pertaining to guanidine-based novel BACE-1 inhibitors for the treatment and maintenance of AD. We have also discussed role of BACE-1 substrates, and its crystal structure, BACE-1 inhibitors in the clinical trial, and essential points to overcome challenges associated with selective development of BACE-1 inhibitors. This paper provides valuable information for the design and discovery of selective new BACE-1 inhibitors against other aspartyl protease enzymes to treat AD.

Automated summary

This paper reviews the use of guanidine-based novel BACE-1 inhibitors for the treatment and maintenance of Alzheimer's disease. Alzheimer's disease is an irreversible neurological disorder, and BACE-1 is an important target for its treatment. Inhibiting BACE-1 can prevent or reverse the progression of the disease.