Innovations in acetylcholinesterase inhibitors: emerging strategies for Alzheimer’s disease therapy (2019–2024)

Abstract

Alzheimer’s disease (AD) is a prevalent irreversible neurological degenerative disorder and one of the considerable health hazards in the aged population worldwide. It is estimated that AD population will reach 74.4 million by 2030, and the prevalence is anticipated to reach 131.5 million by 2050, representing an enormous burden on health organizations. AD is a familiar type of dementia characterized by gradual memory loss and cognitive function impairment. AD is a complex multifactorial disease, and the cholinergic hypothesis is the primary theory explaining its pathogenesis. It was observed that the brains of AD patients showed a sharp decrease in cholinergic neurons and a remarkable deficiency in acetylcholine levels. Thus, acetylcholinesterase inhibitors (AChEI) are considered a promising strategy for AD treatment. The FDA approves four AChEI for AD treatment: tacrine, donepezil, rivastigmine, and galantamine. This review article focuses on the latest advances in the development of new AChEI inhibitors from 2019 to 2024, encompassing single-targeted, multi-targeted, and naturally derived inhibitors as potential treatments for AD. It highlights new molecules with promising inhibitory activity against acetylcholinesterase, underscoring their therapeutic potential in AD management.