{
  "abstract": "Songqiang Cao,1,* Tingting Liu,1,2,* Xiangshu Cheng,1 Xinghua Tian,1 Jianshe Wei11Center for Translational Neurourology, Huaihe Hospital of Henan University, Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng, 475004, People’s Republic of China; 2Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China*These authors contributed this work equallyCorrespondence: Xinghua Tian; Jianshe Wei, Email tianxh@henu.edu.cn; jswei@henu.edu.cnAbstract: Neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) place substantial burden on global public health. Mounting evidence identifies mitochondrial dysfunction as a central contributor to neuronal damage and progressive brain functional decline. As a narrative review, this work aims to dissect mitochondrial‑associated pathological features across these major neurodegenerative disorders, summarize under‑recognized emerging mechanisms, and highlight translational bottlenecks for mitochondrial‑targeted therapies. Mitochondria sustain neuronal survival by mediating oxidative‑phosphorylation‑driven energy production, biomolecule biosynthesis, calcium homeostasis, reactive oxygen species (ROS) metabolism, and apoptotic regulation. In PD, aggregated α‑synuclein (α‑syn) damages respiratory‑chain complex I, perturbs mitochondrial dynamics and blocks PINK1/Parkin‑dependent mitophagy. In AD, amyloid‑β together with hyper‑phosphorylated tau (p-Tau) impairs respiratory complex activity, axonal mitochondrial trafficking and mitophagic clearance. Mutant huntingtin induces multiple mitochondrial lesions in HD, while inflammation‑triggered oxidative stress secondarily compromises mitochondrial function in MS. Pathogenic mutations in ALS disrupt respiratory‑chain assembly, mitochondrial dynamics and mitophagy. Beyond classic mitochondrial defects including respiratory‑chain impairment, dynamic imbalance and defective mitophagy, emerging mechanisms such as mitocytosis, mitochondrial aminoacyl‑tRNA synthetase (mt‑aaRS) dysfunction and mitochondria‑associated membrane (MAM) disruption are discussed. Mitochondrial dysfunction drives neurodegeneration via energy exhaustion, aggravated oxidative stress, pathological protein aggregation and excessive neuronal apoptosis. We further recapitulate mitochondrial‑oriented therapeutic approaches including small‑molecule regulators, mitophagy activators, mitochondrial biogenesis promoters, gene‑editing strategies and mitochondrial transplantation. Notable translational obstacles remain, including limited blood‑brain‑barrier penetration of candidate drugs, narrow therapeutic time‑window post‑symptom onset, and prominent disease heterogeneity. By synthesizing basic experimental findings and pre‑clinical and clinical trial progress, this review provides updated insights into the pathogenesis of neurodegenerative diseases and facilitates the development of precise mitochondrial‑targeted therapeutic regimens.Keywords: neurodegenerative diseases, mitochondrial dysfunctions, oxidative stress, neuronal degeneration, treatment",
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  "affiliations": [
    "School of Life Sciences",
    "Key Laboratory of Neurological Diseases of Kaifeng; Department of Neurology"
  ],
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  "author_total": 5,
  "authors": [
    {
      "name": "Cao S"
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      "name": "Liu T"
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    {
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        1
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      "name": "Cheng X"
    },
    {
      "affs": [
        0
      ],
      "name": "Tian X"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei J"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/08zj5hbrh41g6.bib",
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  "doi": "10.2147/jir.s653025",
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  "pmcid": "PMC13723238",
  "pmid": "42967168",
  "published": "2026-10-27",
  "publisher": "Dove Medical Press",
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      "first_seen": "2026-10-31T14:21:54Z",
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  "title": "The "Invisible Killer” of Neurodegeneration: Mitochondrial Dysfunction in Neurodegenerative Disorders, Mechanisms, Emerging Pathways and Therapeutic Strategies",
  "title_text": "The "Invisible Killer” of Neurodegeneration: Mitochondrial Dysfunction in Neurodegenerative Disorders, Mechanisms, Emerging Pathways and Therapeutic Strategies",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:52Z",
  "url": "https://research.draconitic.com/paper/08zj5hbrh41g6",
  "venue": "Journal of Inflammation Research",
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