A Potent Multi-functional Neuroprotective Derivative of Tetramethylpyrazine

Hai Yun Chen, Da Ping Xu, Guo Lian Tan, Wei Cai, Gao Xiao Zhang, Wei Cui, Jin Zhao Wang, Cheng Long, Ye Wei Sun, Pei Yu, Karl Wahkeung Tsim, Zai Jun Zhang, Yifan Han, Yu Qiang Wang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

28 Citations (Scopus)

Abstract

Neurodegenerative disorders are one of the leading causes of death among the elderly. Therapeutic approaches with a single target have proven unsuccessful in treating these diseases. Structural combination of multi-functional compounds may lead to a molecule with multiple properties. In this study, we designed and synthesized T-006, a novel analog derived from two multi-functional neuroprotective chemicals, tetramethylpyrazine and J147. The methoxyphenyl group of J147 was replaced by tetramethylpyrazine. Bioactivity evaluation showed that T-006 at very low concentrations had multi-functional neuroprotective effects including rescuing iodoacetic acid-induced neuronal loss, preventing oxidative stress-induced neurotoxicity and reducing glutamate-induced excitotoxicity in vitro. Most importantly, T-006 significantly ameliorated memory impairments in APP/PS1 transgenic mice. These multiple functions of a single molecule suggest that T-006 is a promising novel neuroprotective agent for treating various neurodegenerative disorders, including and in particular Alzheimer’s disease.
Original languageEnglish
Pages (from-to)977-987
Number of pages11
JournalJournal of Molecular Neuroscience
Volume56
Issue number4
DOIs
Publication statusPublished - 10 Aug 2015

Keywords

  • J147
  • Multi-functional neuroprotection
  • Neurodegenerative disorders
  • Tetramethylpyrazine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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