Coptisine reverses Alzheimer’s disease by targeting cholinergic and amyloidogenic pathways

Abstract

Alzheimer’s disease (AD) is one of the most unanswered diseases in the world as its complicated pathological mechanism makes it a formidable challenge in modern healthcare with limited intervention options. Due to its chronic nature in neurodegeneration, leading to cognitive decline and brain damage, mitigating this disease is now of major concern globally. The revelation of certain key hallmarks of AD pathology such as cholinergic dysfunction and amyloid plaque toxicity has thrown some insight into identifying therapeutic targets. Only symptomatic relief has been achieved by a single-target therapeutic approach, thus, the development of multi-impediment drugs is urgently needed. The adverse effects of current AD medication and repeated failure of futuristic drugs led us to hunt for a natural compound with beneficial properties that can target multi-facets of AD pathology, and cure this devastating brain disorder. The hypothesis of targeting different pathways contributing to progressive neurodegeneration in AD pathophysiology can be considered a new-age intervention. Coptisine, a bioactive alkaloid with benzyl tetrahydroisoquinoline in structure possesses enormous pharmacological benefits including neuroprotective abilities. Together with the potential of coptisine to inhibit the major targets of AD pathogenesis namely acetylcholinesterase (AChE), beta-secretase (BACE1), and gamma-secretase, this alkaloid can emerge as a new-age multi-target therapeutic for AD. However, robust research on coptisine’s suitability against AD pathogenesis is pivotal considering its therapeutic promises and an unambiguous understanding of the coptisine’s future can be predicted by evaluating its efficacy and safety for ameliorating AD.