A Potent Multi-functional Neuroprotective Derivative of Tetramethylpyrazine

J Mol Neurosci. 2015 Aug;56(4):977-987. doi: 10.1007/s12031-015-0566-x. Epub 2015 May 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Cells, Cultured
  • Hydrazones / chemical synthesis
  • Hydrazones / pharmacology*
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • PC12 Cells
  • Pyrazines / chemical synthesis
  • Pyrazines / chemistry
  • Pyrazines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antioxidants
  • Hydrazones
  • Neuroprotective Agents
  • Pyrazines
  • T-006 compound
  • tetramethylpyrazine