A Potent Multi-functional Neuroprotective Derivative of Tetramethylpyrazine

• Published in: Journal of molecular neuroscience Vol. 56; no. 4; pp. 977 - 987
• Main Authors: Chen, Hai-Yun, Xu, Da-Ping, Tan, Guo-Lian, Cai, Wei, Zhang, Gao-Xiao, Cui, Wei, Wang, Jin-Zhao, Long, Cheng, Sun, Ye-Wei, Yu, Pei, Tsim, Karl Wahkeung, Zhang, Zai-Jun, Han, Yi-Fan, Wang, Yu-Qiang
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2015; Springer Nature B.V
• Subjects: Alzheimer Disease - drug therapy; Alzheimer's disease; Animals; Antioxidants - chemical synthesis; Antioxidants - pharmacology; Antioxidants - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell culture; Cells, Cultured; Chinese medicine; Disease; Hydrazones - chemical synthesis; Hydrazones - pharmacology; Metabolism; Mice; Neurochemistry; Neurology; Neurons - drug effects; Neurons - metabolism; Neuroprotective Agents - chemical synthesis; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Neurotoxicity; Oxidative stress; PC12 Cells; Proteomics; Pyrazines - chemical synthesis; Pyrazines - chemistry; Pyrazines - pharmacology; Rats; Rats, Sprague-Dawley; Transgenic animals; Hong Kong China; United States > US; China; J147; Multi-functional neuroprotection; Tetramethylpyrazine; Neurodegenerative disorders
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-015-0566-x

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.