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Matrix metalloproteinases: potential therapeutic target for diabetic neuropathic pain
Anurag Kuhad1, Pratishtha Singh, Kanwaljit Chopra
1Panjab University, University Institute of Pharmaceutical Sciences, Pharmacology Research Laboratory, UGC Centre of Advanced Study , Chandigarh - 160 014 , India +91 9915173064 ; +91 172 2534101 ; anurag_pu@yahoo.com.
Introduction:
MMPs are zinc-dependent endopeptidases that play a key role in the remodeling of extracellular matrix (ECM). Various pathogenic mediators trigger abnormal MMP activity that leads to ECM abnormality. Hyperglycemia is one of the strong stimuli among oxidative stress and inflammation that upregulate MMP expression in the central and peripheral nervous system. MMP-mediated ECM abnormality hypersensitizes peripheral as well as central nerves that precipitate neuropathic pain in diabetic patients.
Areas Covered:
Molecular mechanisms associated with MMP-mediated diabetic neuropathic pain have been discussed. Various endogenous, natural and synthetic MMP inhibitors are also explored.
Expert Opinion:
In diabetes, hyperglycemia activates MMPs that along with the other pathogenic mediators cause neuronal injury and precipitates neuropathic pain. Thus, MMPs play a crucial role in the development of neuropathic pain among diabetics. However, MMPs are not only responsible for deleterious ECM abnormalities but are also required for beneficial remodeling of ECM under normal physiological conditions. Therefore, highly selective and specific inhibitors must be designed and explored for their clinical potential for treatment/prevention of diabetic neuropathic pain.
Insights
Diabetic neuropathic pain is linked to matrix metalloproteinases (MMPs) activated by hyperglycemia. Targeting MMPs may offer new treatments for this condition.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Matrix metalloproteinases (MMPs) are crucial for extracellular matrix (ECM) remodeling.
- Abnormal MMP activity, often triggered by hyperglycemia, oxidative stress, and inflammation, leads to ECM abnormalities.
- These ECM changes in the nervous system contribute to neuropathic pain in diabetic patients.
Purpose of the Study:
- To discuss the molecular mechanisms of MMP-mediated diabetic neuropathic pain.
- To explore potential MMP inhibitors for therapeutic intervention.
Main Methods:
- Review of molecular mechanisms underlying MMP involvement in diabetic neuropathic pain.
- Exploration of endogenous, natural, and synthetic MMP inhibitors.
Main Results:
- Hyperglycemia activates MMPs, leading to neuronal injury and neuropathic pain.
- MMPs play a significant role in the development and progression of diabetic neuropathic pain.
- MMPs are involved in both pathological ECM abnormalities and physiological ECM remodeling.
Conclusions:
- MMPs are key contributors to diabetic neuropathic pain via hyperglycemia-induced activation and ECM disruption.
- Selective MMP inhibitors are needed for potential clinical application in treating or preventing diabetic neuropathic pain.
- Balancing MMP inhibition for therapeutic benefit while preserving physiological functions is critical.
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