Neurotoxicity and Diabetes: Mechanistic Insights into Oxidative Stress Mediated Neuronal Damage and Potential Neuroprotective Interventions

Kato Jumba K.

Faculty of Science and Technology Kampala International University Uganda

ABSTRACT

Diabetes mellitus is associated with accelerated neuronal injury manifesting as diabetic peripheral neuropathy, cognitive impairment, and heightened risk of neurodegenerative disease. A large body of evidence implicates oxidative stress-the imbalance between production of reactive oxygen and nitrogen species (ROS/RNS) and antioxidant defenses a central mediator linking hyperglycaemia, dyslipidaemia, and chronic inflammation to neuronal dysfunction. Hyperglycaemia-driven metabolic pathways (polyol flux, advanced glycation end-products, protein kinase C activation, hexosamine pathway), mitochondrial overload, NADPH oxidase activation, and inflammation converge on excessive ROS/RNS generation, which in turn damages neuronal macromolecules, perturbs ion homeostasis, impairs axonal transport and mitochondrial dynamics, and triggers neuroinflammation. Translational research has explored a range of neuroprotective strategies tight metabolic control, repurposed antidiabetic drugs with pleiotropic antioxidant effects, nutraceutical and polyphenol interventions, Nrf2 pathway activators, mitochondria-targeted antioxidants, and novel drug-delivery systems-to interrupt the oxidative cascade. While preclinical studies show consistent neuroprotection by redox-targeted interventions, clinical translation has been mixed due to heterogeneity in patient populations, timing of intervention, bioavailability of compounds, and limited biomarker-guided stratification. Future progress requires biomarker-driven trials, mitochondrial- and blood–brain-barrier–targeted delivery, and combination therapies that preserve physiological ROS signalling while preventing pathological oxidative damage. This review synthesizes current mechanistic insights into oxidative stress–mediated neurotoxicity in diabetes and evaluates the evidence and potential of neuroprotective interventions.

Keywords: Diabetes, oxidative stress, neurotoxicity, neuroprotection, mitochondria

 

CITE AS: Kato Jumba K. (2026). Neurotoxicity and Diabetes: Mechanistic Insights into Oxidative Stress Mediated Neuronal

 Damage and Potential Neuroprotective Interventions.

IDOSR JOURNAL OF SCIENCE AND TECHNOLOGY 12(1):61-66. https://doi.org/10.59298/IDOSR/JST/26/113.6166