Diabetic Neuropathy: Review on Molecular Mechanisms

Abstract

: Diabetic mellitus is a worldwide endocrine and metabolic disorder with insulin insensitivity or deficiency or both whose prevalence could rise up to 592 million by 2035. Consistent hyperglycemia leads to one of the most common comorbidities like Diabetic Peripheral Neuropathy (DPN). DPN is underlined with unpleasant sensory experience such as tingling and burning sensation, hyperalgesia, numbness etc. Globally, 50-60% of the diabetic population is suffering from such symptoms like microvascular complication. Consistent hyperglycemia during DM causes activation/inhibition of various pathways playing important role in homeostasis of neurons and other cells. Disruption of these pathways results into apoptosis and mitochondrial dysfunctions causing neuropathy. Among these pathways, pathways like Polyol pathway and PARP pathway are some of the most intensively studied pathways whereas pathways like Wnt pathway, Mitogen activated protein kinase (MAPK), mTOR pathway are comparatively newly discovered. Understanding of these pathways and their role in pathophysiology of DN underlines a few molecules of immense therapeutic value. The inhibitors or activators of these molecules can be of therapeutic importance in management of DPN. This review hence, focuses on these underlying molecular mechanisms intending to provide therapeutically effective molecular targets for treatment of DPN.