Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 176, Issue -, Pages 228-247Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2019.05.020
Keywords
Alzheimer's disease; Multi-target strategy; Acetylcholine esterase; Donepezil; Tacrine
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Funding
- National Natural Science Foundation of China [81874289]
- Double First-Class University project, China Pharmaceutical University [CPU2018GY04]
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Alzheimer's disease (AD) is a multifactorial syndrome resulting in profound misery and poses a substantial burden on human health, economy, and society throughout the world. Based on the numerous AD-related targets in the disease network, multi-target design strategy is a crucial direction to seek for enhanced therapy, and multi-target drugs have the ability to regulate more targets than single-target drugs, affecting the disease network with more potency. Herein, we highlight nine major targets associated with AD, which are acetylcholine esterase (AChE), beta-site amyloid precursor protein cleaving enzyme 1 (beta-secretase, BACE-1), glycogen synthase kinase 3 beta (GSK-3 beta), monoamine oxidases (MAOs), metal ions in the brain, N-methyl-D-aspartate (NMDA) receptor, 5-hydroxytryptamine (5-HT) receptors, the third subtype of histamine receptor (H-3 receptor), and phosphodiesterases (PDEs), and their respective relationship to the disease network. Furthermore, eleven multi-target design strategies classified by the involvement of AChE and related promising compounds for improved therapy of AD in recent years are described based on the nine major targets. (C) 2019 Elsevier Masson SAS. All rights reserved.
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