Oxidative Stress, Neuroinflammation, and Microvascular Damage in Neurodegenerative Diseases: Mechanistic Insights and Therapeutic Approaches

Abstract: Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis share common molecular mechanisms involving oxidative stress, neuroinflammation, and microvascular dysfunction. These interrelated processes form a self-perpetuating cycle that accelerates neuronal loss and cognitive decline. Oxidative stress triggers mitochondrial impairment and lipid peroxidation, while chronic glial activation amplifies the inflammatory milieu through cytokine release and reactive oxygen species generation. Concurrently, endothelial and pericytic injury disrupts the blood–brain barrier (BBB), compromising neurovascular coupling and metabolic homeostasis. This review summarizes the mechanistic crosstalk between oxidative, inflammatory, and vascular pathways in neurodegeneration, highlighting recent advances in antioxidant, anti-inflammatory, and vasoprotective strategies. We further discuss emerging therapeutic approaches such as nanocarrier-based delivery systems, multitarget drugs, and genetic modulation aimed at restoring redox balance and microvascular integrity. Understanding the molecular intersections of these mechanisms may provide new insights into disease-modifying interventions for neurodegenerative disorders.