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Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702
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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-B, AP-1, .

Conclusion

Potential drug targets must be considered for new research on the treatment of neuropathy and nephropathy conditions.

© 2024 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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/content/journals/cmp/10.2174/1874467217666230328084215
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A Detailed Review of Molecular Pathways and Mechanisms Responsible for the Development and Aggravation of Neuropathy and Nephropathy in Diabetes
Curr Mol Pharmacol 17, E280323215026 (2024); https://doi.org/10.2174/1874467217666230328084215
/content/journals/cmp/10.2174/1874467217666230328084215
/content/journals/cmp/10.2174/1874467217666230328084215
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  • Article Type:     Review Article
Keyword(s): Diabetes mellitus; Diabetic nephropathy; NADPH; Nephropathy; Neuroinflammation; Oxidative stress; PKC

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