Mitochondrial Dysfunction as a Driver of Neurodegeneration in Parkinson's and Huntington's Disease: Molecular Insights and Emerging Interventions.

Mitochondrial dysfunction has emerged as a central contributor to the pathogenesis of major neurodegenerative disorders, such as Parkinson's and Huntington's disease. In Parkinson's disease, mitochondrial abnormalities are often linked to mutations in genes like PINK1 and Parkin, which regulate mitochondrial quality control, while α-synuclein aggregation further exacerbates mitochondrial damage. In Huntington's disease, mutant huntingtin protein impairs mitochondrial dynamics, transport, and ATP production, contributing to selective neuronal vulnerability. The convergence of mitochondrial impairments across both diseases highlights a common pathological axis that can be therapeutically targeted. This review critically examines the molecular underpinnings of mitochondrial dysfunction in PD and HD and explores emerging strategies to restore mitochondrial function. These include antioxidants, metabolic modulators, mitophagy activators, and gene therapy approaches. Despite promising preclinical findings, several translational challenges remain, underscoring the need for continued investigation. Understanding the shared and unique mitochondrial-related mechanisms in PD and HD will be essential for developing targeted, disease-modifying therapies that may improve outcomes and quality of life for affected individuals.