Journal
CURRENT NEUROPHARMACOLOGY
Volume 19, Issue 6, Pages 832-867Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1570159X18666200914155951
Keywords
Alzheimer disease; multi-target directed ligands; cholinesterase inhibitors; serotonin transporter; 5-HT receptors; beta - amyloid aggregation; tau protein; monoamine oxidase
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Funding
- FONDECYT [3180602]
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Alzheimer's disease is a common cause of cognitive decline in elderly individuals, with complex and multifactorial etiology. The traditional one drug-one target paradigm is not effective for AD and other complex disorders, highlighting the potential of the multitarget approach in treatment.
Alzheimer's disease (AD) is a chronic, progressive, and fatal neurodegenerative disorder affecting cognition, behavior, and function, being one of the most common causes of mental deterioration in elderly people. Once thought as being just developed because of beta amyloid depositions or neurofibrillary Tau tangles, during the last decades, numerous AD-related targets have been established, the multifactorial nature of AD became evident. In this context, the one drug-one target paradigm has resulted in being inefficient in facing AD and other disorders with complex etiology, opening the field for the emergence of the multitarget approach. In this review, we highlight the recent advances within this area, emphasizing in hybridization tools of well-known chemical scaffolds endowed with pharmacological properties concerning AD, such as curcumin-, resveratrol-, chromone- and indole-. We focus mainly on well established and incipient AD therapeutic targets, AChE, BuChE, MAOs, beta-amyloid deposition, 5-HT 4 and Serotonin transporter, with the aim to shed light about new insights in the AD multitarget therapy.
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