Protective role of IGF-1 and GLP-1 signaling activation in neurological dysfunctions
Protective role of IGF-1 and GLP-1 signaling activation in neurological dysfunctions
复制标题
DOI：
10.1016/j.neubiorev.2022.104896
复制
发表时间：
2022-10-20
影响因子：
8.2
通讯作者：
Rehman, Muneeb U.
中科院分区：
文献类型：
--
作者：
Bhalla, Sonalika;Mehan, Sidharth;Rehman, Muneeb U.
胰岛素样生长因子-1（IGF-1）是一种多效性多肽，在中枢神经系统的发育和成熟中起重要作用。胰高血糖素样肽-1（GLP-1）是一种内源性肠促胰岛素激素，可调节血糖水平和大脑中的脂肪酸氧化。GLP-1也表现出与IGF-1相似的功能和生长因子样特性，这可能是它发挥神经保护作用的方式。最近的临床前和临床证据表明，IGF-1和GLP-1除了调节生长和发育外，还通过调节PI 3/ Akt激酶、哺乳动物雷帕霉素靶蛋白（mTOR）和丝裂原活化蛋白激酶（MAPK/ERK）来预防由淀粉样蛋白生成、脑葡萄糖剥夺、神经炎症和细胞凋亡介导的神经元死亡。IGF-1抵抗和GLP-1缺乏损害保护性细胞信号传导机制，促进神经退行性疾病的进展。在过去的几十年中，IGF-1和GLP-1已成为神经元系统的重要组成部分，并成为几种神经退行性和神经精神功能障碍的潜在治疗靶点。有大量证据表明，IGF-1和GLP-1类似物穿透血脑屏障（BBB），并表现出神经保护功能，包括突触形成，神经元可塑性，蛋白质合成和自噬。总之，这篇综述代表了IGF-1和GLP-1信号靶点激活剂在改善神经系统疾病中的治疗潜力。
Insulin-like growth factor-1 (IGF-1), a pleiotropic polypeptide, plays an essential role in CNS development and maturation. Glucagon-like peptide-1 (GLP-1) is an endogenous incretin hormone that regulates blood glucose levels and fatty acid oxidation in the brain. GLP-1 also exhibits similar functions and growth factor-like prop-erties to IGF-1, which is likely how it exerts its neuroprotective effects. Recent preclinical and clinical evidence indicate that IGF-1 and GLP-1, apart from regulating growth and development, prevent neuronal death mediated by amyloidogenesis, cerebral glucose deprivation, neuroinflammation and apoptosis through modulation of PI3/ Akt kinase, mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK/ERK). IGF-1 resistance and GLP-1 deficiency impair protective cellular signaling mechanisms, contributing to the progression of neurodegenerative diseases. Over the past decades, IGF-1 and GLP-1 have emerged as an essential component of the neuronal system and as potential therapeutic targets for several neurodegenerative and neuropsychiatric dysfunctions. There is substantial evidence that IGF-1 and GLP-1 analogues penetrate the blood-brain barrier (BBB) and exhibit neuroprotective functions, including synaptic formation, neuronal plasticity, protein synthesis, and autophagy. Conclusively, this review represents the therapeutic potential of IGF-1 and GLP-1 signaling target activators in ameliorating neurological disorders.