AChE Inhibition-based Multi-target-directed Ligands, a Novel Pharmacological Approach for the Symptomatic and Disease-modifying Therapy of Alzheimer's Disease

Current Neuropharmacology
Yu WangHong-Zhuan Chen

Abstract

Alzheimer's disease (AD) is the most common form of dementia in elder people, characterised by a progressive decline in memory as a result of an impairment of cholinergic neurotransmission. To date acetylcholinesterase inhibitors (AChEIs) have become the most prescribed drugs for the symptomatic treatment of mild to moderate AD. However, the traditional "one molecule-one target" paradigm is not sufficient and appropriate to yield the desired therapeutic efficacy since multiple factors, such as amyloid-β (Aβ) deposits, neuroinflammation, oxidative stress, and decreased levels of acetylcholine (ACh) have been thought to play significant roles in the AD pathogenesis. New generation of multi-target drugs is earnestly demanded not only for ameliorating symptoms but also for modifying the disease. Herein, we delineated the catalytic and non-catalytic functions of AChE, and summarized the works of our group and others in research and development of novel AChEI-based multi-target-directed ligands (MTDLs), such as dual binding site AChEIs and multitarget AChEIs inhibiting Aβ aggregation, regulating Aβ procession, antagonizing platelet-activating factor (PAF) receptor, scavenging oxygen radical, chelating metal ions, inhibiting monoamine...Continue Reading

Citations

Dec 15, 2016·Expert Opinion on Therapeutic Patents·Stanton F McHardyMatthew C Valdez
Nov 24, 2017·Metallomics : Integrated Biometal Science·Nilda V BarbosaJoão B T Rocha
Jul 1, 2020·Fundamental & Clinical Pharmacology·Adel A GomaaMariam A Nicola
Dec 28, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Yao ChenHaopeng Sun
Jan 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sofia BenfeitoFernanda Borges
Oct 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lucie CahlíkováLubomír Opletal
Jan 3, 2020·Current Medicinal Chemistry·Ting YangHailin Cong
Feb 12, 2021·Bioorganic Chemistry·Pritam ThapaMukut Sharma
Jul 15, 2021·Pathology Oncology Research : POR·Yanzhi BiYang Ling
Dec 7, 2018·ACS Chemical Neuroscience·Huan Wang, Haiyan Zhang
Jul 17, 2019·ACS Chemical Neuroscience·Dushyant V PatelMange Ram Yadav

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Methods Mentioned

BETA
X-ray
transgenic

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