Neuroinflammation and Oxidative Stress in Diabetic Neuropathy: Futuristic Strategies Based on These Targets

Figure 1

Pathophysiology of diabetic neuropathy. Hyperglycemia activates numerous metabolic pathways like polyol pathway, protein kinase c (PKC) pathway, advanced glycation end products (AGE) pathway, and hexosamine pathway. All these pathways are known to integrate through hyperglycemia mediated mitochondrial ROS production. Oxidative stress and these classical pathways in combination activate transcription factors such as nuclear factor kappa enhancer of B cells (NF-κB) and speciality protein-1 (SP-1), resulting in neuroinflammation and vascular impairment. Further, these pathways combined with dysfunctional mitochondria mediated apoptosis or bioenergetic depletion can lead to neuronal damage lading to DN. Poly-ADP ribose polymerase (PARP) mediated NADH/ATP depletion can lead to neuronal dysfunction due to failure of various energy dependent processes in neurons. (ERK: extracellular related kinase, IL-6: interleukin-6, iNOS: inducible nitric oxide synthase, COX-2: cyclooxygenase-2, TGF-β: transforming growth factor-β, and PAI-1: plasminogen activator inhibitor-1.)