4.5 Review

Multitarget Directed Ligand Approaches for Alzheimer's Disease: A Comprehensive Review

Journal

MINI-REVIEWS IN MEDICINAL CHEMISTRY
Volume 21, Issue 16, Pages 2361-2388

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1389557521666210405161205

Keywords

Alzheimer's disease; acetylcholinesterase; butyrylcholinesterase; monoamine oxidase; beta secretase; amyloid plaques; donepezil; tacrine

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Alzheimer's disease is a multifactorial neurodegenerative disease without a cure, leading researchers to develop multi-target drugs. Current treatments are palliative and an effective drug for AD is still in the process of discovery.
Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disease, and a drug which targets a single protein would not provide a cure for this disease. Currently available drugs for AD are all palliative rather than curative. FDA approved only five drugs for the treatment of AD, which include tacrine, donepezil, galantamine, rivastigmine, and memantine. Tacrine has been discontinued due to its hepatotoxicity. The lack of therapeutic effectiveness of the single-target drugs and multifactorial etiology of AD have led to the design of multitarget directed ligands for AD. Objective: The researchers in this field are constantly making efforts to develop a drug which may prove to be the exact cure for this disease by exploring the different biological targets associated with AD. The present review comprises various multitarget approaches and tools used for finding out a lead compound or a new drug, which will provide a cure for AD. Methods: We have scrutinized and reviewed 75 research articles published in various peer reviewed journals in the last two decades in the field of multi target directed ligand approaches for the discovery of a new therapeutic agent for AD. Results: The review highlights the recent advances in the field of AD research and shows that the battle for the discovery of an effective drug for AD is in process and AD still remains an incurable disease for which treatment is just palliative. Conclusion: The review might be helpful for researchers working on multi target directed ligands against AD.

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