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.

Comparative Efficacy of East Asian Herbal Formulae Containing Astragali Radix–Cinnamomi Ramulus Herb-Pair against Diabetic Peripheral Neuropathy and Mechanism Prediction: A Bayesian Network Meta-Analysis Integrated with Network Pharmacology

“…Increased levels of MAPKs are also involved in the pathogenesis of DPN via inflammatory cytokines via the activation of c-Jun/JNK. Therefore, the inhibitory effect of the ACP on this mechanism is significant because activation of MAPKs contributes to the overall progression of DPN [ 131 ]. Additionally, neuroinflammation and neurodegeneration are important pathologies in diabetic complications including DPN.…”

Acrolein-inducing ferroptosis contributes to impaired peripheral neurogenesis in zebrafish

“…Up to now, several processes such as oxidative stress, inflammation, increased activity of polyol pathway, an increase of protein glycosylation products, and disturbance of lipid metabolism are widely recognized as contributing to the development of DPN (Callaghan et al, 2015(Callaghan et al, , 2016(Callaghan et al, , 2018Sanaye and Kavishwar, 2023). However, the molecules which mediate Beneficial effects of anti-acrolein (ACR), but not hypoglycemic treatment on motor neuron development in ACR treated embryos.…”

Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment

“…The oxidative stress and extracellular stimuli, such as Ca 2+ generated by upstream pathways, can stimulate the phosphorylation of MAPKs and activate the MAPK pathway. In addition to acting as a downstream pathway, hyperglycemia may directly cause phosphorylation of MAPKs ( Figure 3 ) ( 132 , 133 ). A study on peripheral neuropathy caused by paclitaxel showed that MAPK signaling pathways such as JNK, ERK1/2, and nuclear factors- κB played a major role in it ( 134 ).…”