siRNA targeting PARP-1 alleviates diabetic peripheral neuropathy in a streptozotocin-induced rat model

Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes mellitus, affecting nearly 50% of diabetic patients and leading to chronic pain, numbness and progressive sensory and motor function loss. This study investigates the potential of siRNA-mediated silencing of poly(ADP-rib...

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Bibliographic Details
Published in:Journal of drug targeting 2024-12, p.1-12
Main Authors: Moqbel Redhwan, Moqbel Ali, M G, Hariprasad, Samaddar, Suman, Bafail, Duaa, Hard, Sumaia Abdulbari Ahmed Ali, Guha, Sourav, Dhavale, Apurwa
Format: Article
Language:English
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Summary:Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes mellitus, affecting nearly 50% of diabetic patients and leading to chronic pain, numbness and progressive sensory and motor function loss. This study investigates the potential of siRNA-mediated silencing of poly(ADP-ribose) polymerase 1 (PARP1) to alleviate DPN in a rat model. PARP1 overactivation, driven by hyperglycaemia-induced oxidative stress, exacerbates neuronal damage in DPN. Using chitosan nanoparticles (ChNPs) to deliver PARP1-targeting siRNA intrathecally in diabetic rats induced with streptozotocin (STZ) 55 mg/kg intraperitoneally, we conducted behavioural and physiological assessments, including Sciatic Functional Index (SFI), motor nerve conduction velocity (MNCV), grip strength and pain sensitivity tests, alongside qRT-PCR analyses, to evaluate therapeutic outcomes. Our findings indicate statistically significant improvements, with siRNA ChNPs-mediated PARP1 silencing alleviating neuropathic symptoms in DPN rats (  
ISSN:1061-186X
1029-2330
1029-2330
DOI:10.1080/1061186X.2024.2431316