Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, 142001, India.
Neurol Sci. 2021 Aug;42(8):3145-3166. doi: 10.1007/s10072-021-05328-6. Epub 2021 May 21.
The prominent causes for motor neuron diseases like ALS are demyelination, immune dysregulation, and neuroinflammation. Numerous research studies indicate that the downregulation of IGF-1 and GLP-1 signaling pathways plays a significant role in the progression of ALS pathogenesis and other neurological disorders. In the current review, we discussed the dysregulation of IGF-1/GLP-1 signaling in neurodegenerative manifestations of ALS like a genetic anomaly, oligodendrocyte degradation, demyelination, glial overactivation, immune deregulation, and neuroexcitation. In addition, the current review reveals the IGF-1 and GLP-1 activators based on the premise that the restoration of abnormal IGF-1/GLP-1 signaling could result in neuroprotection and neurotrophic effects for the clinical-pathological presentation of ALS and other brain diseases. Thus, the potential benefits of IGF-1/GLP-1 signal upregulation in the development of disease-modifying therapeutic strategies may prevent ALS and associated neurocomplications.
肌萎缩侧索硬化症等运动神经元疾病的突出病因是脱髓鞘、免疫失调和神经炎症。许多研究表明，IGF-1 和 GLP-1 信号通路的下调在 ALS 发病机制和其他神经疾病的进展中起着重要作用。在本综述中，我们讨论了 IGF-1/GLP-1 信号在 ALS 等神经退行性表现中的失调，如遗传异常、少突胶质细胞降解、脱髓鞘、胶质细胞过度激活、免疫失调和神经兴奋。此外，本综述还揭示了基于 IGF-1 和 GLP-1 激活剂的前提，即恢复异常的 IGF-1/GLP-1 信号可能导致 ALS 和其他脑部疾病的临床病理表现的神经保护和神经营养作用。因此，IGF-1/GLP-1 信号上调在疾病修饰治疗策略的发展中的潜在益处可能预防 ALS 和相关的神经并发症。
