Abstract

UNRAVELING DIABETIC NEUROPATHY: KEY TARGETS AND NOVEL THERAPEUTIC INSIGHTS

Vandana S. Nade, *Divya A. Patil, Priyanka J. Hemake, Laxman A. Kawale, Vaishanvi A. Ahire and Vaishanvi B. Nikam

ABSTRACT

Diabetic neuropathy (DN) is a prevalent and debilitating complication of diabetes mellitus, affecting approximately 50% of diabetic patients globally. With the rising prevalence of diabetes, the burden of DN is grown significantly, particularly in developing countries. Epidemiological studies revealed that DN is more common in individuals with type 2 diabetes and longer disease duration, with nearly 10% of patients exhibiting symptoms at the time of diagnosis. Globally, DN accounts for up to 27% of direct healthcare costs associated with diabetes, making it a significant public health challenge. The pathogenesis of DN involves complex mechanisms, including hyperglycaemia-induced oxidative stress, chronic inflammation, and metabolic dysfunction, leading to progressive nerve damage. This review highlights key molecular pathways implicated in DN, such as Advanced Glycation End Products (AGEs), aldose reductase, Protein Kinase C (PKC), Poly (ADP-Ribose) Polymerase (PARP), Transient Receptor Potential Vanilloid-1 (TRPV1), Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), Vascular Endothelial Growth Factor (VEGF), and Neurotrophin-3 (NT-3). Targeting these pathways present innovative therapeutic opportunities to treat DN at its root. Strategies such as AGE inhibitors, aldose reductase inhibitors, and PARP inhibitors aim to alleviate oxidative stress and inflammation, while modulators of TRPV1, VEGF, and NT-3 show promise in enhancing nerve repair and reducing neuropathic pain. The review emphasizes the need for innovative approaches that combine molecular targeting, gene therapy, and advanced pharmacological strategies to combat DN effectively. By addressing the underlying mechanisms, such treatments could transform DN management, providing not only symptom relief but also long-term disease modification.

Keywords: Advanced glycation end-product (AGEs), Chronic inflammation, Diabetic neuropathy (DN), Mitochondrial dysfunction.