Interconnected Roles of Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation in Alzheimer’s Disease: Mechanistic Insights and Therapeutic Implications
1. Chinonso Linda, University of Lagos, Nigeria, Student, Nigeria
2. Amina obasogie, Ahmadu Bello University, Nigeria, Professor, Nigeria
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, synaptic dysfunction, and neuronal loss. While amyloid-beta plaques and tau neurofibrillary tangles are classical pathological hallmarks, increasing evidence demonstrates that oxidative stress, mitochondrial dysfunction, and neuroinflammation are central drivers of disease progression. Oxidative imbalance leads to lipid peroxidation, protein oxidation, and DNA damage, contributing to neuronal vulnerability. Mitochondrial dysfunction impairs energy metabolism and enhances reactive oxygen species production, further aggravating cellular injury. Concurrently, chronic microglial activation sustains inflammatory responses and amplifies oxidative damage. These interrelated processes create a self-propagating cycle that accelerates neurodegeneration. Understanding their molecular interactions provides new opportunities for therapeutic intervention. This review synthesizes current findings on oxidative stress, mitochondrial abnormalities, and neuroinflammatory mechanisms in AD and highlights emerging treatment strategies targeting these interconnected pathways.
Alzheimer’s disease oxidative stress mitochondrial dysfunction neuroinflammation microglial activation reactive oxygen species (ROS) neurodegeneration inflammatory cytokines
Oxidative stress, mitochondrial dysfunction, and neuroinflammation are deeply interconnected processes that play central roles in Alzheimer’s disease pathogenesis. Rather than acting independently, these mechanisms form a pathological network that drives neuronal degeneration and cognitive decline. A comprehensive understanding of their molecular interplay is essential for developing effective disease-modifying therapies. Future therapeutic strategies should adopt multi-targeted approaches to interrupt the vicious cycle of oxidative damage, bioenergetic failure, and chronic inflammation, offering renewed hope for individuals affected by Alzheimer’s disease.
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The author confirms sole responsibility for the following: study conception and design, data collection, analysis and interpretation of results, and manuscript preparation.
The authors did not receive any specific grants from funding agencies in the public, commercial, or non-profit sectors for the research, authorship, and/or publication of this article.
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There are no conflicts of interest to report from any of the authors.
I thank the following individuals for their expertise and assistance in all aspects of our study and for their help in writing the manuscript. I am also grateful for the insightful comments given by anonymous peer reviewers. Everyone's generosity and expertise have improved this study in myriad ways and saved me from many errors.
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