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

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

Abstract

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

Citation

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. https://doi.org/10.1016/j.ejmech.2019.05.020

• 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
• DOI: https://doi.org/10.1016/j.ejmech.2019.05.020
• Keywords: Alzheimer's disease; Multi-target strategy; Acetylcholine esterase; Donepezil; Tacrine
• Public URL: https://nottingham-repository.worktribe.com/output/2257706
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0223523419304295?via%3Dihub
• Contract Date: Jul 6, 2019