期刊
JOURNAL OF MOLECULAR NEUROSCIENCE
卷 56, 期 4, 页码 977-987出版社
HUMANA PRESS INC
DOI: 10.1007/s12031-015-0566-x
关键词
Neurodegenerative disorders; Multi-functional neuroprotection; Tetramethylpyrazine; J147
资金
- China 12.5 Innovative Drug Project [2012ZX09103-101-055]
- Hong Kong Scholars Program [122870]
- China Postdoctoral Science Foundation [2012T50748, 2013M531911]
- Research Grants Council of Hong Kong [561011, 15101014]
- Hong Kong Polytechnic University [G-U952, G-YM32, G-SB10, G-YZ15]
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 multifunctional 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.
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