Cited by 758Genetic Neurodegenerative DiseasesMitochondrial Function and PathologyMetabolism and Genetic Disorders

Mitochondrial defect in Huntington's disease caudate nucleus

Gu, M., Gash, M. T., Mann, V. M., Javoy‐Agid, F., Cooper, J. M., Schapira, A. H. V.·1996·Annals of Neurology

Abstract

Although the Huntington's disease (HD) gene defect has been identified, the structure and function of the abnormal gene product and the pathogenetic mechanisms involved in producing death of selective neuronal populations are not understood. Indirect evidence from several sources indicates that a defect of energy metabolism and consequent excitotoxicity are involved in HD. Toxin models of HD may be induced by 3‐nitropropionic acid or malonate, both inhibitors of succinate dehydrogenase, complex II of the mitochondrial respiratory chain. We analyzed mitochondrial respiratory chain function in the caudate nucleus (n = 10) and platelets (n = 11) from patients with HD. In the caudate nucleus, severe defects of complexes II and III (53–59%, p < 0.0005) and a 32–38% ( p < 0.01) deficiency of complex IV activity were demonstrated. No deficiencies were found in platelet mitochondrial function. The mitochondrial defect identified in HD caudate parallels that induced by HD neurotoxin models and further supports the role of abnormal energy metabolism in HD. The relationship of the mitochondrial defect to the role of huntingtin is not known.

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Crossref · 10.1002/ana.410390317

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  • Biochemical studies revealed reduced activity of several key components of oxidative phosphorylation and the TCA cycle, including complexes II-III and aconitase, in advanced stage HD patients, while complex-I activity was unaltered.

    “Biochemical studies revealed reduced activity of several key components of oxidative phosphorylation and the TCA cycle, including complexes II-III and aconitase, in advanced stage HD patients, while complex-I activity was unaltered40-43.”

    From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [41]

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Authors
Gu, M., Gash, M. T., Mann, V. M., Javoy‐Agid, F., Cooper, J. M., & Schapira, A. H. V.
Affiliations
The Royal Free Hospital (GB)
Corresponding author
Schapira, A. H. V.
Venue
Annals of Neurology
Publisher
Wiley
Published
1996-03
Volume
39
Issue
3
Pages
385-389
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
OpenAlex
W2139826556
Cited by
758
References
19
Citations by year
2026: 10 · 2025: 13 · 2024: 13 · 2023: 20 · 2022: 19 · 2021: 28 · 2020: 19 · 2019: 22 · 2018: 28 · 2017: 10 · 2016: 26 · 2015: 23 · 2014: 25 · 2013: 31 · 2012: 44
FWCI
8.20
Type
journal article
Language
en
Open access
closed
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
Huntington's disease, caudate nucleus, mitochondrial respiratory chain, complex II, cytochrome bc1 complex, cytochrome c oxidase, succinate dehydrogenase, energy metabolism, excitotoxicity, 3-nitropropionic acid, malonate, platelets, neuronal cell death
MeSH terms
Aged, Caudate Nucleus, Chromosomes, Human, Pair 4, DNA, Mitochondrial, Energy Metabolism, Humans, Huntington Disease, Middle Aged, RNA, Messenger, Electron Transport Complex III, Gene Expression, NAD(P)H Dehydrogenase (Quinone), Glutamic Acid, Culture Techniques

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