Mutant huntingtin
The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease
... LAMP1 is a type I transmembrane glycoprotein and a marker of lysosomes and autolysosomes [24], organelles critical for downstream steps of the autophagy cascade. While not a core macroautophagy protein, LAMP1 is a ...
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Oral administration of the cannabigerol derivative VCE 003 2 promotes subventricular zone neurogenesis and protects against mutant huntingtin induced neurodegeneration
... of mutant hun- tingtin (htt) protein with expanded glutamine repeats in the N-terminal portion of the protein ...[1]. Mutant htt ex- pression induces striatal atrophy and medium spiny neuron (MSN) death, ...
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Increased 90-kDa ribosomal S6 kinase (Rsk) activity is protective against mutant huntingtin toxicity
... the huntingtin (htt) gene [15], and characterized by the preferential neurodegen- eration of striatal medium-sized spiny neurons ...full-length mutant huntingtin (mhtt) (STHdh Q111/Q111 ) show ...
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Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington’s disease patients
... however, mutant huntingtin protein (mHTT), the cause of Huntington’s disease (HD), is at very low levels in CSF and, to our knowledge, has never been measured ...
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Mutant huntingtin impairs immune cell migration in Huntington disease
... of mutant huntingtin (htt) compromises the normal functions of immune ...a mutant htt fragment in microglial cell lines was sufficient to reproduce these defi- ...expressing mutant htt had a ...
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Reduction of mutant huntingtin accumulation and toxicity by lysosomal cathepsins D and B in neurons
... toxic mutant huntingtin is essential in order to explore thera- peutic strategies against Huntington ’ s ...against mutant huntingtin ...process huntingtin protein in the absence of the ...
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Preventing mutant huntingtin proteolysis and intermittent fasting promote autophagy in models of Huntington disease
... Huntington disease (HD) is caused by the expression of mutant huntingtin (mHTT) bearing a polyglutamine expansion. In HD, mHTT accumulation is accompanied by a dysfunction in basal autophagy, which ...
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Nrf2 Activation by Dimercaptopropanol Attenuates Mutant Huntingtin Toxicity
... level mutant HTT (mHTT) aggregates perturb cellular metabolism, intracellular trafficking and mitochondrial function, resulting in the increased production of reactive oxygen species (ROS) an event closely linked ...
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Inducible mutant huntingtin expression in HN10 cells reproduces Huntington's disease-like neuronal dysfunction
... Cellular models of HD are essential for studying the biol- ogy of mutant Htt. Non-neuronal primary cells from HD patients have been used to study CAG-repeat instability [19] or calcium homeostasis [20]. PC12-cell ...
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Mutant huntingtin induces iron overload via up-regulating IRP1 in Huntington’s disease
... Background: Iron accumulation in basal ganglia accompanies neuronal loss in Huntington’s disease (HD) patients and mouse disease models. Disruption of HD brain iron homeostasis occurs before the onset of clinical signs. ...
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Domain Organization of Mutant Huntingtin Fibrils
... 152 to increased caspase and calpain activation and enhanced production of toxic N‐ terminal fragments in the HD brain Majumder et al., 2007. These fragments are degraded by addition[r] ...
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The transrepression arm of glucocorticoid receptor signaling is protective in mutant huntingtin-mediated neurodegeneration
... 8 tunicamycin-mediated transcriptional changes, only a limited subset of genes induced by tunicamycin was maximally decreased by both mometasone and GRT10 (Figure 4A). Of these genes, the induction of growth ...
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GLP-1 Analogue Liraglutide Attenuates Mutant Huntingtin-Induced Neurotoxicity by Restoration of Neuronal Insulin Signaling
... induced oxidative stress is related to impaired neuronal insulin signaling and is a deleterious factor 178. that increases neurotoxicity[r] ...
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Lack of interleukin-1 type 1 receptor enhances the accumulation of mutant huntingtin in the striatum and exacerbates the neurological phenotypes of Huntington's disease mice
... result, mutant htt is abundantly expressed in neuronal cells in the cortex and striatum of N171-82Q mice, causing motor function defi- cits, body weight loss, and early death that often occurs at 5-6 months in ...
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Deimmunization for gene therapy: host matching of synthetic zinc finger constructs enables long-term mutant Huntingtin repression in mice
... Results: After rAAV vector delivery, we found that non-self proteins induce significant inflammatory responses in the brain, in agreement with previous studies. Specifically, microglial cells were activated at 4 and 6 ...
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ROCK-phosphorylated vimentin modifies mutant huntingtin aggregation via sequestration of IRBIT
... Next, we aimed to identify the mechanism, by which vimentin levels and phosphorylation modifies accumula- tion and aggregation of pathogenic Htt. Our hypothesis on vimentin affecting polyQ aggregation in cooperation with ...
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Serine 421 regulates mutant huntingtin toxicity and clearance in mice
... expansion in the N-terminal region of the protein huntingtin (HTT). There are no cures or disease-modifying therapies for HD. HTT has a highly conserved Akt phosphorylation site at serine 421, and prior work in HD ...
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Mutant huntingtin fragmentation in immune cells tracks Huntington’s disease progression
... the huntingtin (HTT) protein (1). Mutant HTT (mHTT) expression in the CNS is the primary pathogenic factor for the development of HD, with increasing expression levels associated with disease severity and ...
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Genetic and pharmacological inhibition of calcineurin corrects the BDNF transport defect in Huntington's disease
... of mutant huntingtin in vitro and in vivo ...of mutant huntingtin at the S421 residue promotes neuro- protection in HD, by restoring huntingtin function in the transport of BDNF ...
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RNAi mechanisms in Huntington’s disease therapy: siRNA versus shRNA
... Huntington ’ s Disease (HD) is a genetically dominant trinucleotide repeat disorder resulting from CAG repeats within the Huntingtin (HTT) gene exceeding a normal range (> 36 CAGs). Symptoms of the disease ...
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