Title:A Detailed Review of Molecular Pathways and Mechanisms Responsible for the
Development and Aggravation of Neuropathy and Nephropathy in Diabetes
Volume: 17
Author(s): Phool Chandra, Neetu Sachan, Nikita Saraswat*Niraj Vyawahare
Affiliation:
- Dr. D. Y Patil College of Pharmacy, Akurdi, Pune, Maharashtra-411044, India
Keywords:
Diabetes mellitus, Diabetic nephropathy, Nephropathy, NADPH, Oxidative stress, PKC, Neuroinflammation.
Abstract:
Background:
Diabetic mellitus is responsible for triggering many conditions, such as neuropathy, nephropathy, and retinopathy. Hyperglycemia leads to the
development of oxidative stress conditions, activation of pathways, and generation of metabolites, leading to complications like neuropathy and
nephropathy.
Objective:
This paper aims to discuss the mechanism of actions, pathways, and metabolites triggered due to the development of neuropathy and nephropathy
post-long-haul diabetes in patients. The therapeutic targets are also highlighted, proving to be a potential cure for such conditions.
Methods:
Research works were searched from international and national databases with keywords like “diabetes,” “diabetic nephropathy,” “NADPH,”
“oxidative stress,” “PKC,” “Molecular mechanisms,” “ cellular mechanisms,” “complications of diabetes,” and “factors.” The databases searched
were PubMed, Scopus, Directory of open access journals, Semantic Scholar, Core, Europe PMC, EMBASE, Nutrition, FSTA- Food Science and
Technology, Merck Index, Google Scholar, PubMed, Science Open, MedlinePlus, Indian citation index, World Wide Science, and Shodhganga.
Results:
Pathways causing protein kinase C (PKC) activation, free radical injury, oxidative stress, and aggravating the conditions of neuropathy and
nephropathy were discussed. In diabetic neuropathy and nephropathy, neurons and nephrons are affected to the extent that their normal physiology
is disturbed, thus leading to further complications and conditions of loss of nerve sensation in diabetic neuropathy and kidney failure in diabetic
nephropathy.
Current treatment options available for the management of diabetic neuropathy are anticonvulsants, antidepressants, and topical medications,
including capsaicin. According to AAN guidelines, pregabalin is recommended as the first line of therapy, whereas other drugs currently used for
treatment are gabapentin, venlafaxine, opioids, amitriptyline, and valproate.
Drug targets for treating diabetic neuropathy must suppress the activated polyol pathways, kinase C, hexosamine, and other pathways, which
amplify neuroinflammation. Targeted therapy must focus on the reduction of oxidative stress and proinflammatory cytokines and suppression of
neuroinflammation, NF-κB, AP-1, etc.
Conclusion:
Potential drug targets must be considered for new research on the treatment of neuropathy and nephropathy conditions.
