Molecular Basis of Neurodegeneration and Therapies in Diabetic Neuropathy

Abstract

Neuropathy is one among the known disorders corresponding diabetes. The biochemical mechanisms of this devastating neurodegenerative disorder of diabetic neuropathy (DN) have not yet clearly understood. DN is loss of function nerves beginning distally in the lower extremities that is also characterized by pain and substantial morbidity. It leads to distressing and expensive clinical complications such as foot ulceration, leg amputation, and neuropathic pain. Despite countless promising therapeutic research efforts, effective drugs are still lacking for the treatment of DN. Therefore, current review emphasizes on complications and therapeutic strategies which could be effective in DN. Various search engines like Google Scholar, PubMed, SpringerLink, Medline and Science direct were used for accessing different articles of world-wide journals to harness the information of previous work done with our relevance. Databases like PDB and NCBI were used to understand molecular information of proteins and DNA in DN. In present review, we discussed causes, mechanisms that lead to promotion of DN and possible therapies of DN. The information provided in this review provide research gap to investigators to understand molecular mechanisms underlying DN and to attempt natural substances as possible effective therapy. Current review discusses significant research gaps for making an attempt to investigate a successful natural product and its molecular target for DN. We also accentuate the use of natural product instead of a synthetic drug for treatment of DN. Diabetes Mellitus; IDF: International Diabetes Federation; PKC: Protein Kinase C; AGEs: Advanced Glycation End Products; GSK: Glycogen Synthase Kinase; DSP: Distal Symmetric Polyneuropathy; DSPN: Distal symmetric polyneuropathy; EDIC: Epidemiology of Diabetes Interventions and Complications; DCCT: Diabetes Control and Complications Trial; AND: Autonomic Diabetic Neuropathy; CAN: Cardiac Autonomic Neuropathy; ED: Erectile Dysfunction; ROS: Reactive Oxygen Species; ER: Endoplasmic Reticulum; DPN: Diabetic Peripheral Neuropathy; SDH: Sorbitol Dehydrogenase; NO: Nitric Oxide; ARI: Aldose Reductase