Mitochondrial Dysfunction as a Central Mechanism in Neurodegenerative Disorders

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BSTRACT

Mitochondrial impairment underpins the pathological cascade in most major neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis. Disrupted bioenergetics, excessive reactive oxygen species, altered mitochondrial dynamics, and defects in mitophagy collectively drive neuronal loss and synaptic failure in affected brain regions. Recent advances elucidate the crosstalk between genetic, metabolic, and inflammatory signaling with mitochondrial dysfunction, opening new horizons for diagnostics and mitochondrial-targeted therapy. This review integrates molecular, clinical, and therapeutic insights, providing a robust framework for future disease modification strategies.