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

Author(s): Yu Wang, Hao Wang, Hong-zhuan Chen.

Journal Name: Current Neuropharmacology

Volume 14 , Issue 4 , 2016

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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 oxidase B (MAO-B), blocking N-methyl-D-aspartic acid (NMDA) receptor and others.

Keywords: Acetylcholinesterase inhibitor, alzheimer’s disease, multi-target-directed ligand.

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Article Details

VOLUME: 14
ISSUE: 4
Year: 2016
Page: [364 - 375]
Pages: 12
DOI: 10.2174/1570159X14666160119094820
Price: $58

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