Emerging Neuroprotective Strategies Against Oxidative Stress-Induced Neurotoxicity in Systemic Disorders: Lessons from Diabetes, Malaria, and Hepatic Dysfunction

Mutebi Mark

Department of Pharmacology Kampala International University Uganda

Email: mark.mutebi@studwc.kiu.ac.ug

ABSTRACT

Oxidative stress is a central, converging mechanism underlying neurotoxicity in a broad range of systemic disorders, including diabetes mellitus, malaria, and hepatic dysfunction. In these conditions, excessive reactive oxygen and nitrogen species (ROS/RNS), impaired antioxidant defenses, mitochondrial dysfunction, and neuroinflammation interact to damage neurons and glia, disrupt the blood–brain barrier (BBB), and impair synaptic and cognitive function. Understanding shared molecular pathways allows cross-fertilization of therapeutic strategies. This review synthesizes current knowledge on oxidative-stress–driven neural injury across diabetes, cerebral malaria, and liver disease, and evaluates emerging neuroprotective strategies: direct and indirect antioxidants, Nrf2 pathway modulators, mitochondrial-targeted therapies, anti-inflammatory and immunomodulatory agents, BBB-stabilizing approaches, nanodelivery systems, metabolic and lifestyle interventions, and regenerative/repair modalities. Preclinical advances-such as mitochondria-targeted peptides, Nrf2 activators, and nanoparticle-facilitated delivery of antioxidants-show promise, and some repurposed drugs (metformin, statins) demonstrate pleiotropic effects across disorders. However, translation is challenged by disease heterogeneity, timing of therapy relative to injury, limited CNS penetration, and inadequate biomarkers. We highlight priority areas for translational research: combination regimens that target oxidative stress and inflammation simultaneously, precision delivery systems to cross or protect the BBB, robust biomarkers for oxidative injury and therapeutic response, and early-intervention trials in stratified patient populations. Integrating mechanistic insights from diabetes, malaria, and hepatic dysfunction can accelerate development of broadly applicable neuroprotective strategies that mitigate oxidative-stress–mediated neural injury in systemic disease.

Keywords: Oxidative stress, neuroprotection, diabetes, cerebral malaria, hepatic encephalopathy

CITE AS: Mutebi Mark (2026). Emerging Neuroprotective Strategies Against Oxidative Stress-Induced Neurotoxicity in Systemic Disorders: Lessons from Diabetes, Malaria, and Hepatic Dysfunction. IAA Journal of Scientific Research 13(1):78-82. https://doi.org/10.59298/IAAJSR/2026/1317882