ER Stress-Induced eIF2-alpha Phosphorylation Underlies Sensitivity of Striatal Neurons to Pathogenic Huntingtin [PDF]
, 2013 A hallmark of Huntington's disease is the pronounced sensitivity of striatal neurons to polyglutamine-expanded huntingtin expression. Here we show that cultured striatal cells and murine brain striatum have remarkably low levels of phosphorylation of ...
Ashery, U. +6 more
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The ubiquitin-proteasome pathway in Huntington's disease. [PDF]
, 2008 The accumulation of mutant protein is a common feature of neurodegenerative disease. In Huntington's disease, a polyglutamine expansion in the huntingtin protein triggers neuronal toxicity.
Finkbeiner, Steven, Mitra, Siddhartha
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Therapeutic Antisense Targeting of Huntingtin [PDF]
DNA and Cell Biology, 2020 Antisense oligonucleotides (ASOs) are a relatively new therapeutic entity that utilizes short chemically modified strands of DNA in targeted interactions with RNA to modulate the type or amount of resultant protein. This brief review summarizes the preclinical, translational, and early clinical development of an ASO designed to reduce the production of
Smith, AV, Tabrizi, SJ
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N17 Modifies mutant Huntingtin nuclear pathogenesis and severity of disease in HD BAC transgenic mice. [PDF]
, 2015 The nucleus is a critical subcellular compartment for the pathogenesis of polyglutamine disorders, including Huntington's disease (HD). Recent studies suggest the first 17-amino-acid domain (N17) of mutant huntingtin (mHTT) mediates its nuclear exclusion
Barth, Albert M +13 more
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Wild-Type Huntingtin Reduces the Cellular Toxicity of Mutant Huntingtin In Vivo [PDF]
The American Journal of Human Genetics, 2001 We have developed yeast artificial chromosome (YAC) transgenic mice expressing normal (YAC18) and mutant (YAC46 or YAC72) human huntingtin (htt), in a developmental- and tissue-specific manner, that is identical to endogenous htt. YAC72 mice develop selective degeneration of medium spiny projection neurons in the lateral striatum, similar to what is ...
Julian A. Guttman +6 more
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Imbalance of p75(NTR)/TrkB protein expression in Huntington's disease: Implication for neuroprotective therapies [PDF]
, 2013 Neuroprotective therapies based on brain-derived neurotrophic factor (BDNF) administration have been proposed for Huntington's disease (HD) treatment. However, our group has recently reported reduced levels of TrkB in HD mouse models and HD human brain ...
Alberch, J. +5 more
core +1 more source
Sphingomyelin and GM1 Influence Huntingtin Binding to, Disruption of, and Aggregation on Lipid Membranes [PDF]
, 2018 Huntington disease (HD) is an inherited neurodegenerative disease caused by the expansion beyond a critical threshold of a polyglutamine (polyQ) tract near the N-terminus of the huntingtin (htt) protein. Expanded polyQ promotes the formation of a variety
Campbell, Warren A. +5 more
core +4 more sources
Intrabodies Binding the Proline-Rich Domains of Mutant Huntingtin Increase Its Turnover and Reduce Neurotoxicity [PDF]
, 2008 Although expanded polyglutamine (polyQ) repeats are inherently toxic, causing at least nine neurodegenerative diseases, the protein context determines which neurons are affected.
Bugg, Charles W. +5 more
core +2 more sources
Huntingtin: Here, There, Everywhere!
Journal of Huntington's Disease, 2013 Huntingtin is the protein mutated in Huntington disease, a dominant inherited neurodegenerative disorder. Huntingtin is ubiquitously expressed throughout the body, however its role outside the central nervous system has been overlooked. This review focuses on the peripheral distribution of huntingtin.
Sandrine Humbert +1 more
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MeCP2: a novel Huntingtin interactor [PDF]
Human Molecular Genetics, 2013 Transcriptional dysregulation has been proposed to play a major role in the pathology of Huntington's disease (HD). However, the mechanisms that cause selective downregulation of target genes remain unknown. Previous studies have shown that mutant huntingtin (Htt) protein interacts with a number of transcription factors thereby altering transcription ...
McFarland KN +7 more
openaire +5 more sources