The anti-dementia drug candidate, (-)-clausenamide, improves memory impairment through its multi-target effect

Shifeng Chu, Shaolin Liu, Wenzhen Duan, Yong Cheng, Xueying Jiang, Chuanjiang Zhu, Kang Tang, Runsheng Wang, Lin Xu, Xiaoying Wang, Xiaoming Yu, Kemei Wu, Yan Wang, Muzou Wang, Huiyong Huang, Juntian Zhang

Research output: Contribution to journalReview article

Abstract

Multi-target drugs, such as the cocktail therapy used for treating AIDS, often show stronger efficacy than single-target drugs in treating complicated diseases. This review will focus on clausenamide (clau), a small molecule compound originally isolated from the traditional Chinese herbal medicine, Clausenalansium. The finding of four chiral centers in clau molecules predicted the presence of 16 clau enantiomers, including (-)-clau and (+)-clau. All of the predicted enantiomers have been successfully synthesized via innovative chemical approaches, and pharmacological studies have demonstrated (-)-clau as a eutomer and (+)-clau as a distomer in improving cognitive function in both normal physiological and pathological conditions. Mechanistically, the nootropic effect of (-)-clau is mediated by its multi-target actions, which include mild elevation of intracellular Ca2+ concentrations, modulation of the cholinergic system, regulation of synaptic plasticity, and activation of cellular and molecular signaling pathways involved in learning and memory. Furthermore, (-)-clau suppresses the pathogenesis of Alzheimer's disease by inhibiting multiple etiological processes: (1) beta amyloid protein-induced intracellular Ca2+ overload and apoptosis and (2) tau hyperphosphorylation and neurodegeneration. In conclusion, the nature of the multi-target actions of (-)-clau substantiates it as a promising chiral drug candidate for enhancing human cognition in normal conditions and treating memory impairment in neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)179-187
Number of pages9
JournalPharmacology and Therapeutics
Volume162
DOIs
StatePublished - Jun 1 2016

Keywords

  • Calcium
  • Chirality
  • Clausenamide
  • Dementia
  • Long-term potentiation
  • Signaling pathway

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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  • Cite this

    Chu, S., Liu, S., Duan, W., Cheng, Y., Jiang, X., Zhu, C., Tang, K., Wang, R., Xu, L., Wang, X., Yu, X., Wu, K., Wang, Y., Wang, M., Huang, H., & Zhang, J. (2016). The anti-dementia drug candidate, (-)-clausenamide, improves memory impairment through its multi-target effect. Pharmacology and Therapeutics, 162, 179-187. https://doi.org/10.1016/j.pharmthera.2016.01.002