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Multi-target design strategies for the improved treatment of Alzheimer's disease

Zhang, Pengfei; Xu, Shengtao; Zhu, Zheying; Xu, Jinyi


Pengfei Zhang

Shengtao Xu

Associate Professor in International Pharmacy and Traditional Medicines

Jinyi Xu


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 (?-secretase, BACE-1), glycogen synthase kinase 3 beta (GSK-3?), 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 (H3 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.


Zhang, P., Xu, S., Zhu, Z., & Xu, J. (2019). Multi-target design strategies for the improved treatment of Alzheimer's disease. European Journal of Medicinal Chemistry, 176, 228-247.

Journal Article Type Article
Acceptance Date May 6, 2019
Online Publication Date May 11, 2019
Publication Date Aug 15, 2019
Deposit Date Jul 6, 2019
Publicly Available Date May 12, 2020
Journal European Journal of Medicinal Chemistry
Print ISSN 0223-5234
Electronic ISSN 1768-3254
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 176
Pages 228-247
Keywords Alzheimer's disease; Multi-target strategy; Acetylcholine esterase; Donepezil; Tacrine
Public URL
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