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Cited by 109Genetic Neurodegenerative DiseasesHereditary Neurological DisordersGenetic factors in colorectal cancer

PGC-1alphaas modifier of onset age in Huntington disease

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Taherzadeh-Fard, Elahe, Saft, Carsten, Andrich, Jürgen, Wieczorek, Stefan, Arning, Larissa·2009·Molecular Neurodegeneration
DOI 10.1186/1750-1326-4-10PMC PMC2644307
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Abstract

Although there is a strong correlation between CAG repeat length and age at onset (AO) of motor symptoms, individual Huntington disease (HD) patients may differ dramatically in onset age and disease manifestations despite similar CAG repeat lengths. This has led to a search for genetic factors that influence AO. In order to identify such a genetic modifier, we analysed polymorphisms in the PGC-1alpha gene. Recent data indicate inhibition of PGC-1alpha function by mutant Htt supporting a link between transcriptional deregulation and mitochondrial dysfunction in HD. In > 400 HD patients, a polymorphism located within intron 2, a potential recombination hot spot, explains a small, but statistically significant, amount of the variability in AO. Our data suggest that PGC-1alpha has modifying effects on the pathogenic process in HD.

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  • PGC-1α downregulation has been associated with extensive alterations in several metabolic pathways, particularly oxidative phosphorylation and the mitochondrial electron transport chain.

    “PGC-1␣ downregulation has been associated with extensive alterations in several metabolic pathways, particularly in oxidative phosphorylation and the mitochondrial electron transport chain (Cui et al., 2006;Taherzadeh-Fard et al., 2009).”

    From Human ApoE Isoforms Differentially Modulate Brain Glucose and Ketone Body Metabolism: Implications for Alzheimer's Disease Risk Reduction and Early Intervention (2018) · cites this paper as Taherzadeh-Fard et al., 2009

    The Findings section (page not specified) reports that mutant huntingtin inhibits PGC-1α function and links this to mitochondrial dysfunction in Huntington disease. It also says PGC-1α regulates mitochondrial respiration, but does not describe extensive alterations across metabolic pathways or specifically identify oxidative phosphorylation and the electron transport chain as altered. (LLM, conf=0.84)

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Authors
Taherzadeh-Fard, E., Saft, C., Andrich, J., Wieczorek, S., & Arning, L.
Affiliations
  • Ruhr University Bochum (DE)
  • St. Josef-Hospital (DE)
Corresponding author
Arning, Larissa
ORCID
Arning, Larissa
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2009-02-06
Volume
4
Issue
1
Pages
10-10
ISSN
1750-1326 (ISSN-L)
DOI
10.1186/1750-1326-4-10
PMC
PMC2644307
OpenAlex
W2048927290
Cited by
109
References
1
Citations by year
2025: 3 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 7 · 2014: 10 · 2013: 11 · 2012: 15
FWCI
6.00
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Neurodegeneration (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords
Huntington's disease, PGC-1α, age of onset, genetic modifiers, CAG repeat length, intron 2 polymorphism, recombination hotspots, mutant huntingtin, mitochondrial dysfunction, transcriptional dysregulation

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