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Loss of Huntingtin-Mediated BDNF Gene Transcription in Huntington's Disease
TLDR
It is demonstrated that wild-type huntingtin up-regulates transcription of brain-derived neurotrophic factor (BDNF), a pro-survival factor produced by cortical neurons that is necessary for survival of striatal neurons in the brain. Expand
Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease.
TLDR
The natural history of HD-related changes in the YAC128 mice has been defined, demonstrating the presence of huntingtin inclusions after the onset of behavior and neuropathological changes and making it an ideal mouse model for the assessment of neuroprotective and other therapeutic interventions. Expand
Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines
TLDR
It is shown that lymphoblast mitochondria from patients with HD have a lower membrane potential and depolarize at lower calcium loads than do mitochondriaFrom controls, and mitochondrial calcium abnormalities occur early in HD pathogenesis and may be a direct effect of mutant huntingtin on the organelle. Expand
Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes
TLDR
It is concluded that wild-type huntingtin acts in the cytoplasm of neurons to regulate the availability of REST/NRSF to its nuclear NRSE-binding site and that this control is lost in the pathology of Huntington disease. Expand
Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin
TLDR
Treatment of transgenic mice expressing a yeast artificial chromosome containing 128 CAG repeats with low-dose memantine blocks extrasynaptic (but not synaptic) NMDARs and ameliorates neuropathological and behavioral manifestations, and offers a rational therapeutic approach for protecting susceptible neurons in Huntington's disease. Expand
A YAC Mouse Model for Huntington’s Disease with Full-Length Mutant Huntingtin, Cytoplasmic Toxicity, and Selective Striatal Neurodegeneration
TLDR
These mice demonstrate that initial neuronal cytoplasmic toxicity is followed by cleavage of htt, nuclear translocation of htt N-terminal fragments, and selective neurodegeneration, clearly showing that aggregates are not essential to initiation of neuronal death. Expand
Detection of Huntington’s disease decades before diagnosis: the Predict-HD study
TLDR
The findings from the Predict-HD study suggest the approximate time scale of measurable disease development, and suggest candidate disease markers for use in preventive HD trials. Expand
A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease
TLDR
The peripheral immune system was examined and found widespread evidence of innate immune activation detectable in plasma throughout the course of HD, suggesting parallel central nervous system and peripheral pathogenic pathways of immune activation in HD. Expand
Mutations in HFE2 cause iron overload in chromosome 1q–linked juvenile hemochromatosis
TLDR
The positional cloning of the locus associated with juvenile hemochromatosis is reported and the identification of a new gene crucial to iron metabolism is identified, now called HFE2, whose protein product the authors call hemojuvelin. Expand
Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes
TLDR
The studies show that the HD gene is essential for postimplantation development and that it may play an important role in normal functioning of the basal ganglia. Expand
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