神经细胞黏附分子衍生肽FGL药理作用研究进展

Research progress in function and pharmacology of neural cell adhesion molecule-derived peptide FG loop

神经细胞黏附分子(NCAM)具有诱导神经新生、促进神经分化、保护神经细胞等生物学功能,对于神经系统的发育和功能起着关键性调节作用。FGL是根据NCAM的空间结构和其与成纤维细胞生长因子受体的结合位点设计的含15个氨基酸的生物活性多肽。作为NCAM的功能核心片段,FGL除了可保护神经、诱导神经分化外,还具备抗炎和调节神经可塑性等多种药理作用,在缺血性脑损伤、老年认知障碍、阿尔茨海默病和抑郁症等神经精神疾病的治疗应用上显现出巨大的价值。不仅如此,临床试验结果显示,FGL对人体是安全的,阿尔茨海默病的临床Ⅰ期试验正在进行中。FGL极有可能成为用于治疗神经精神疾病的有效药物,具有广阔的临床应用前景。

Neural cell adhesion molecules （NCAMs） are able to promote neurogenesis, neuronal differentiation, and neuronal protection, playing a pivotal role in the regulation of the development and functions of the nervous system. FG Ioop（FGL）, a bioactive polypeptide composed of 15 amino acids, is developed according to the spatial structure of NCAMs and binding site with fibroblast growth factor receptors. As the functional core segment of NCAMs, FGL has been proved to be neuroprotective, promote neuronal differentiation, have anti-inflammatory effects and regulate neural plasticity, which has a great potential in treatment of various neuropsychiatric diseases, such as ischemic brain injury, cognitive disorder, Alzheimer disease （AD） and depression. Furthermore, clinical researches have demonstrated that FGL is well tolerated in healthy male volunteers with no safety concerns. Phase I clinical trial of FGL for AD is underway. FGL may be a potential therapeutic agent for treatment of human neuropsychiatric diseases in the future, which shows a promisinq application.