Mechanism-driven multitarget therapeutics for diabetic peripheral neuropathy

Diabetic Peripheral Neuropathy (DPN) is one of the most common chronic complications of diabetes. Clinical characteristics of DPN include symmetrical paresthesia, pain and progressive impairment of nerve function, which seriously affects patients' quality of life. Currently, the treatment of DPN remains challenging due to its complex pathogenesis, highlighting an urgent need for the development of effective drugs based on new therapeutic strategies and targets. This review systematically summarizes the complex pathogenic mechanisms of DPN, which involve the interplay of oxidative stress, mitochondrial dysfunction, chronic neuroinflammation, and deficiency in neurotrophic factors. We also discuss recent progress in multi-target drug development, analyzing the mechanisms and clinical potential of several agent classes, such as antioxidants, anti-inflammatory drugs, nerve regeneration promoters, and microcirculation modulators. By integrating current insights into mechanisms and treatment approaches, this review aims to provide a useful perspective on multi-target strategies for DPN.