Diabetic Neuropathy: Its Pathogenesis and Therapeutic Drug Targets

Diabetic neuropathy is the one of the most common complication which occurs in 60% of the patients suffering from diabetes. Extensive research has identified some major pathways which lead to micro-vascular complications in diabetes. Study of these pathways for the progression of the disease and their interconnections with other pathways may guide us to develop therapeutic regime for its treatment. Reactive oxygen species are reported to be one of the main important causes for diabetic neuropathy, and mitochondrial generation of reactive oxygen species in response to hyperglycemic conditions has also been considered as a contributor to oxidative stress. The increased level of oxidative stress results in the over-activation of poly ADP-ribose polymerase (PARP), as well as of NF- κB. Other than reactive oxygen species, there are many pathogenetic pathways which are involved with this complication. Some of the pathways responsible for the dreaded disease are: advanced glycation end product formation, protein kinase C, NF-κB activation and increased polyol flux. These pathways can further lead to increased cellular oxidative damage to organelles and biomolecules, causing dysregulation of cellular functions. In turn, it also leads to the production of a number of other factors which again increase the malfunction of the neurovascular system. Present article describes few important pathways responsible for diabetic neuropathy, aiming towards the proper understanding of their interlinks with other pathways, which can bring forth new drug target sites and can result in the discovery of potentially new and better therapeutics.