The Energetics of Huntington's Disease

@article{Browne2004TheEO,
  title={The Energetics of Huntington's Disease},
  author={Susan E. Browne and M. Flint Beal},
  journal={Neurochemical Research},
  year={2004},
  volume={29},
  pages={531-546}
}
Huntington's disease (HD) is a hereditary neurodegenerative disorder that gradually robs sufferers of the ability to control movements and induces psychological and cognitive impairments. This devastating, lethal disease is one of several neurological disorders caused by trinucleotide expansions in affected genes, including spinocerebellar ataxias, dentatorubral-pallidoluysian atrophy, and spinal bulbar muscular atrophy. HD symptoms are associated with region-specific neuronal loss within the… 
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References

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Apoptosis in Huntington's disease
Oxidative Stress in Huntington's Disease
TLDR
Findings of elevated levels of oxdative damage products in areas of degeneration in HD brain, and of increased free radical production in animal models, indicate the involvement of oxidative stress either as a causative event, or as a secondary constituent of the cell death cascade in the disease.
A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice.
TLDR
Analysis of the mutation introduced into the endogenous mouse Hdh gene reveals significant levels of germline instability, which implies that effective treatment of HD may require an understanding and amelioration of these dysfunctional processes, rather than simply preventing the premature death of neurons in the brain.
Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse
Huntington's disease is a progressive neurodegenerative disease caused by an abnormally expanded (>36) CAG repeat within the ITI5 gene encoding a widely expressed 349‐kd protein, huntingtin. The
Neuroprotective Effects of Creatine in a Transgenic Mouse Model of Huntington's Disease
TLDR
Nuclear magnetic resonance spectroscopy showed that creatine supplementation significantly increased brain creatine concentrations and delayed decreases in N-acetylaspartate concentrations, supporting a role of metabolic dysfunction in a transgenic mouse model of HD and suggesting a novel therapeutic strategy to slow the pathological process.
Biochemical abnormalities and excitotoxicity in Huntington's disease brain
TLDR
It is proposed that NO• generation produces a graded response, with aconitase inhibition followed by complex II/III inhibition and the initiation of a self‐amplifying cycle of free radical generation and acon itase inhibition, which results in severe ATP depletion, which is critical steps in the pathogenesis of HD.
Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates.
TLDR
Findings show that chronic administration of 3-NP to nonhuman primates can replicate many of the characteristic motor and histologic features of HD, further strengthening the possibility that a subtle impairment of energy metabolism may play a role in its pathogenesis.
Transgenic rat model of Huntington's disease.
TLDR
A rat model transgenic of HD is generated, which carries a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter, which is the first transgenic rat model of a neurodegenerative disorder of the brain.
Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease.
TLDR
The effects of creatine administration in a transgenic mouse model of HD produced by 82 polyglutamine repeats in a 171 amino acid N-terminal fragment of huntingtin significantly improved survival, slowed the development of motor symptoms, and delayed the onset of weight loss.
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