Saha Priya, Yarra Sai Sumanjali, Arruri Vijay, Mohan Utpal, Kumar Ashutosh
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER) SAS Nagar, Sec 67, Mohali, Punjab, 160062, India.
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) Kolkata, Maniktala Main Road, Kolkata, West Bengal, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb;398(2):1129-1144. doi: 10.1007/s00210-024-03422-y. Epub 2024 Sep 9.
Diabetic neuropathy (DN) is one of the major microvascular complications of diabetes mellitus affecting 50% of the diabetic population marred by various unmet clinical needs. There is a need to explore newer pathological mechanisms for designing futuristic regimens for the management of DN. There is a need for post-transcriptional regulation of gene expression by non-coding RNAs (ncRNAs) to finetune different cellular mechanisms with significant biological relevance. MicroRNAs (miRNAs) are a class of small ncRNAs (~ 20 to 24 nucleotide length) that are known to regulate the activity of ~ 50% protein-coding genes through repression of their target mRNAs. Differential expression of these miRNAs is associated with the pathophysiology of diabetic neuropathy via regulating various pathways such as neuronal hyperexcitability, inflammation, axonal growth, regeneration, and oxidative stress. Of note, the circulating and extracellular vesicular miRNAs serve as potential biomarkers underscoring their diagnostic potential. Recent pieces of evidence highlight the potential of miRNAs in modulating the initiation and progression of DN and the possibility of developing miRNAs as treatment options for DN. In this review, we have elaborated on the role of different miRNAs as potential biomarkers and emphasized their druggable aspects for promising future therapies for the clinical management of DN.
糖尿病神经病变(DN)是糖尿病的主要微血管并发症之一,影响着50%的糖尿病患者,存在各种未满足的临床需求。有必要探索新的病理机制,以设计未来治疗DN的方案。非编码RNA(ncRNAs)对基因表达进行转录后调控,以微调具有重要生物学意义的不同细胞机制。微小RNA(miRNAs)是一类小的ncRNAs(长度约为20至24个核苷酸),已知通过抑制其靶mRNA来调节约50%的蛋白质编码基因的活性。这些miRNAs的差异表达通过调节各种途径,如神经元过度兴奋、炎症、轴突生长、再生和氧化应激,与糖尿病神经病变的病理生理学相关。值得注意的是,循环和细胞外囊泡miRNAs作为潜在的生物标志物,突出了它们的诊断潜力。最近的证据强调了miRNAs在调节DN的发生和发展方面的潜力,以及将miRNAs开发为DN治疗选择的可能性。在这篇综述中,我们阐述了不同miRNAs作为潜在生物标志物的作用,并强调了它们在未来有望用于DN临床管理的治疗方面的可靶向性。