Therapeutic potential of Nrf-2 pathway in the treatment of diabetic neuropathy and nephropathy.

Type 2 diabetes (T2D) is one of the most widely spread metabolic disordersand is also referred as a 'lifestyle' disorder. According toa study conducted by IDB, the number of individuals affected with diabetes is expected to increase from 463 to 700 million by the end of year 2045. Thus, there is a great need to developed targeted therapies that can maintain homeostasis of glucose levels and improving insulin sensitivity which can overcome hurdles associated with conventional medicine. Detailed analysis was conducted by analyzing various research and review papers which were searched using MEDLINE and EMBASE using various keywords. This search retrieved the most appropriate content on these molecules targeting Nrf-2 functions and Nrf-2 pathway associated with diabetic neuropathy and nephropathy. In this review article, we have highlighted the role of Nrf-2 in diabetic associated complications of neuropathy and nephropathy. Since hyperglycemia is associated with oxidative stress and inflammation, regulating Nrf-2 activity through various synthetic and natural activators whichmay provide therapeutic benefits for the treatment and mitigation of diabetic neuropathy and nephropathy as well. Based on the available literature on Nrf-2 activity and despite some controversies in the association of Nrf-2 activity and its therapeutic usage, it can be concluded that regulation of this pathway is a trigger in the development of diabetes-associated complications. Thus, targeting this pathway with various activators may emerge as a novel therapy in the treatment of diabetes and diabetes-associated complications. Nrf-2 activation leading to regulation of various downstream pathways responsible for managament of Diabetic neuropathy and nephropathy Legend: Activities regulated by the activation of Nrf-2 pathway by Natural and Synthetic activators. Various downstream signalling pathway are involved in increase (+) and decrease (-) in levels of Nrf-2 levels. Subsequently controlling various mechanism involved in the pathogenies of Diabetic neuropathy and nephropathy.