Journal Article

Mitochondrial Dysfunction in Neurodegenerative Diseases

Yang, Han-Mo

2025

Overview

Mitochondrial dysfunction represents a pivotal characteristic of numerous neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. These conditions, distinguished by unique clinical and pathological features, exhibit shared pathways leading to neuronal damage, all of which are closely associated with mitochondrial dysfunction. The high metabolic requirements of neurons make even minor mitochondrial deficiencies highly impactful, driving oxidative stress, energy deficits, and aberrant protein processing. Growing evidence from genetic, biochemical, and cellular investigations associates impaired electron transport chain activity and disrupted quality-control mechanisms, such as mitophagy, with the initial phases of disease progression. Furthermore, the overproduction of reactive oxygen species and persistent neuroinflammation can establish feedforward cycles that exacerbate neuronal deterioration. Recent clinical research has increasingly focused on interventions aimed at enhancing mitochondrial resilience—through antioxidants, small molecules that modulate the balance of mitochondrial fusion and fission, or gene-based therapeutic strategies. Concurrently, initiatives to identify dependable mitochondrial biomarkers seek to detect pathological changes prior to the manifestation of overt symptoms. By integrating the current body of knowledge, this review emphasizes the critical role of preserving mitochondrial homeostasis as a viable therapeutic approach. It also addresses the complexities of translating these findings into clinical practice and underscores the potential of innovative strategies designed to delay or potentially halt neurodegenerative processes.

• Publisher: MDPI AG,MDPI
• Subject: Aging / Alzheimer's disease / Amyotrophic lateral sclerosis / Animals / Biomarkers / Biosynthesis / Carbohydrates / Clinical trials / Cytochrome / Dehydrogenases / Electron transport chain / Enzymes / Fatty acids / Gene expression / Health care / Homeostasis / Humans / Huntingtons disease / Kinases / Metabolites / Mitochondria / Mitochondria - metabolism / Mitochondria - pathology / Mitochondrial DNA / mitochondrial dynamics / mitochondrial dysfunction / Mitophagy / Neurodegeneration / neurodegenerative disease / Neurodegenerative diseases / Neurodegenerative Diseases - metabolism / Neurodegenerative Diseases - pathology / Oxidative Stress / Parkinson's disease / Permeability / Proteins / Quality control / Reactive oxygen species / Reactive Oxygen Species - metabolism / Review