Abstract

POTENTIAL ROLE OF AUTOPHAGY MODULATORS IN THE PROGRESSION OF DIABETIC NEUROPATHY

Shiwani Rajput*, Nidhi Sharma, Ritu Dahiya and Sheetal Rajput

.

Abstract

Diabetic peripheral neuropathy (DPN) is a prevalent consequence of diabetes, affecting 50- 60% of diabetic individuals and substantially influencing global amputation rates. The pathogenesis of diabetic peripheral neuropathy (DPN) encompasses many pathways, including the buildup of extracellular matrix proteins, neuroinflammation, axonal degeneration, and the loss of unmyelinated fibers, resulting in sensory conduction delays and nerve injury. Hyperglycemia significantly contributes to this illness by its impact on oxidative-nitrosative stress, mitochondrial dysfunction, and demyelination. Current FDA-approved therapies for neuropathic pain in diabetic peripheral neuropathy (DPN), such as duloxetine and pregabalin, largely focus on neurotransmitter pathways but exhibit limited effectiveness due to the disease's multifactorial characteristics. This research investigates the possibility of autophagy regulation as a treatment approach for diabetic peripheral neuropathy (DPN), emphasizing its function in cellular quality control and the reclamation of damaged components. The processes of autophagy, encompassing macroautophagy, chaperone-mediated autophagy, and microautophagy, are examined concerning their relevance in the etiology of diabetic neuropathy. The research analyses the correlation between protein misfolding, oxidative stress, and endoplasmic reticulum dysfunction in diabetes, highlighting the potential of augmenting autophagic mechanisms to alleviate these impacts. The function of the ubiquitin-proteasome system in protein breakdown and cellular homeostasis is also examined. The findings indicate that targeting autophagy and associated pathways may provide novel strategies for managing diabetic peripheral neuropathy, necessitating additional exploration of pharmacological compounds capable of successfully modulating these processes.

Keywords: Hyperglycemia, macroautophagy, neuroinflammation.