A Potent Multi-functional Neuroprotective Derivative of Tetramethylpyrazine
A Potent Multi-functional Neuroprotective Derivative of Tetramethylpyrazine
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DOI：
10.1007/s12031-015-0566-x
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发表时间：
2015-08-01
影响因子：
3.1
通讯作者：
Wang, Yu-Qiang
中科院分区：
文献类型：
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作者：
Chen, Hai-Yun;Xu, Da-Ping;Wang, Yu-Qiang
神经退行性疾病是老年人死亡的主要原因之一。事实证明，单一靶点的治疗方法在治疗这些疾病方面并不成功。多官能团化合物的结构组合可能导致分子具有多种性质。在本研究中，我们设计并合成了一种新型类似物T-006，该类似物来源于两种多功能神经保护剂川芎嗪和J147。J147的甲氧基苯基被川芎嗪取代。生物活性评价显示，极低浓度的T-006在体外具有多种神经保护作用，包括挽救碘乙酸诱导的神经元丢失、防止氧化应激诱导的神经毒性和减轻谷氨酸诱导的兴奋性毒性。最重要的是，T-006显著改善了APP/PS1转基因小鼠的记忆损伤。单分子的这些多重功能表明，T-006是一种很有前途的新型神经保护剂，可用于治疗各种神经退行性疾病，包括特别是阿尔茨海默病。
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.