Xing Qi-Chang, Chen Jia, Liu Zheng, Li Wen-Can, Liu Xiang, Li Wei
Department of Clinical Pharmacy, Xiangtan Central Hospital (The Affiliated Hospital of Hunan University), Xiangtan 411100, Hunan Province, China.
World J Diabetes. 2025 Jun 15;16(6):105709. doi: 10.4239/wjd.v16.i6.105709.
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes and is characterized by sensory and motor impairments resulting from neural injury. Schwann cells (SCs), which are important for peripheral nerve function, are compromised under hyperglycemic conditions, leading to impaired axonal regeneration and demyelination. Autophagy, a cellular degradation process, is essential for SC function and significantly influences DPN progression. This article highlights the significance of autophagy in SCs and its potential as a pharmacotherapeutic target in DPN. We discuss the mechanisms of autophagy in SCs, including the mammalian target of rapamycin, adenosine monophosphate-activated protein kinase, and phosphatase and tensin homolog-induced putative kinase/parkin pathways, and their dysregulation in DPN. This article also examines various natural products and chemical agents that modulate autophagy and enhance the efficacy of DPN treatment. These agents target key signaling pathways, such as adenosine monophosphate-activated protein kinase/mammalian target of rapamycin and demonstrate potential in promoting nerve regeneration and restoring SC function. The roles of exosomes, long non-coding RNA, and proteins in the regulation of autophagy have also been explored. In conclusion, targeting autophagy in SCs is a promising strategy for DPN treatment and offers new insights into therapeutic interventions. Further research is warranted to fully exploit these targets for clinical applications.
糖尿病周围神经病变(DPN)是糖尿病常见的并发症,其特征是神经损伤导致的感觉和运动功能障碍。雪旺细胞(SCs)对周围神经功能至关重要,在高血糖条件下会受到损害,导致轴突再生受损和脱髓鞘。自噬是一种细胞降解过程,对雪旺细胞功能至关重要,并显著影响DPN的进展。本文强调了自噬在雪旺细胞中的重要性及其作为DPN药物治疗靶点的潜力。我们讨论了雪旺细胞中自噬的机制,包括雷帕霉素哺乳动物靶点、腺苷单磷酸激活蛋白激酶以及磷酸酶和张力蛋白同源物诱导的假定激酶/帕金途径,以及它们在DPN中的失调。本文还研究了各种调节自噬并提高DPN治疗效果的天然产物和化学试剂。这些试剂靶向关键信号通路,如腺苷单磷酸激活蛋白激酶/雷帕霉素哺乳动物靶点,并在促进神经再生和恢复雪旺细胞功能方面显示出潜力。还探讨了外泌体、长链非编码RNA和蛋白质在自噬调节中的作用。总之,针对雪旺细胞中的自噬是一种有前景的DPN治疗策略,并为治疗干预提供了新的见解。有必要进行进一步研究以充分利用这些靶点用于临床应用。