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Huntington's Disease - Astrophysics Data System

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Last Updated: 11 May 2022

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Changes in striatal procedural memory coding correlate with learning deficits in a mouse model of Huntington disease

Early cognitive impairments in the striatum and cortex during degeneration have been predicted in hereditary neurodegenerative Huntington disease, before motor deficits can be attributed to striatum and cortex dysfunction. These findings reveal vital information on the in vivo cellular processes in the corticostriatal pathway, in which the HD mutation confers its effects on cognitive skills in early HD.

Source link: https://ui.adsabs.harvard.edu/abs/2011PNAS..108.9280C/abstract


A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model

neurons seem to be less responsive to classic autophagy inducers than nonneuronal cells, although autophagy promotes the clearance of misfolded protein and has been thus suggested as a protein therapy for proteinopathies. We found an N 10 -substituted phenozine that in proper doses and safely upregulated neurophagy in neurons in an Akt- and mTOR-independent manner. This protein, which was also neuroprotective and reduced the accumulation of diffuse and aggregated misfolded protein in a neuron model of HD. This pharmacope may be useful in investigating autophagy in neurons as well as in the development of neurodegenerative proteinopathies.

Source link: https://ui.adsabs.harvard.edu/abs/2010PNAS..10716982T/abstract


Transcriptional control of amino acid homeostasis is disrupted in Huntington's disease

According to nutritional strain, antioxidant supplementation restores the diminished ATF4 response to nutrient stress. Multiple degenerative processes in HD are governed by a molecular link between amino acid disposition and oxidative stress. Agents that restore cysteine balance may have therapeutic value.

Source link: https://ui.adsabs.harvard.edu/abs/2016PNAS..113.8843S/abstract


Deletion of SUMO1 attenuates behavioral and anatomical deficits by regulating autophagic activities in Huntington disease

SUMO protein can decorate other proteins by a process called SUMOylation that may reduce the toxicity of proteins related to neurodegenerative diseases. The mutant huntingtin protein in Huntington disease degenerates nerve cells, and SUMOylation of mHTT makes it more soluble and more toxic to nerve cells. We show that SUMO deletion in a humanized mouse HD model depletes mHTT and prevents brain shrinkage and behavioral abnormalities.

Source link: https://ui.adsabs.harvard.edu/abs/2022PNAS..11907187R/abstract


Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington's disease

In both tested ages and reduced visceral adiposity as compared to BACHD mice in all tested conditions, as well as reduced visceral adiposity at 6 months of age, according to our findings. Our preliminary findings show that mGluR5 deficiency in BACHD mice leads to weight gain and visceral adiposity, as well as a decrease in the inflammatory state in the visceral adipose tissue, which may indicate that mGluR5 may play a role in adiposity modulation.

Source link: https://ui.adsabs.harvard.edu/abs/2022NatSR..12.5621S/abstract


Dysregulation of dopamine receptor D2 as a sensitive measure for Huntington disease pathology in model mice

The ability to quantitatively assess the effects of a proposed medical intervention for Huntington disease in animal models of the disease is a significant step toward the development of a more effective therapy for the disease's devastating neurodegenerative disorder. We present here an option that integrates a cell-based assay's quantitative precision and general link to molecular functions with the ability to specifically monitor effects in HD model mouse neurons. A highly reproducible time course of reporter expression is observed for four genetic models and one viral model. This quantitative assessment of HD pathology can be used to determine the effects of HD therapeutics in small cohorts with high optimism. We further demonstrate that adding an shRNA against the huntingtin transgene by virus will raise this pathological status in medium spiny neurons transplanted with the construct.

Source link: https://ui.adsabs.harvard.edu/abs/2012PNAS..109.7487C/abstract


Impaired inhibitory GABAergic synaptic transmission and transcription studied in single neurons by Patch-seq in Huntington's disease

Although the genetic basis of HD is known, neuronal dysfunction remains unclear, the molecular mechanisms underlying neuronal dysfunction are uncertain. We find a number of genes whose expression changes are linked to physiological abnormalities in mutant Htt neurons. We show that pharmacological inhibition of an epigenetic regulator rectifies several functional, morphological, and transcriptional defects in mutant neurons.

Source link: https://ui.adsabs.harvard.edu/abs/2021PNAS..11820293P/abstract


Huntington disease arises from a combinatory toxicity of polyglutamine and copper binding

Dietary copper intervention also modifies HD phenotypes in the fly. Huntingtin can cause both the copper-facilitated toxicity as well as the copper-independent polyQ toxicity, according to our findings, and it means that an appropriate HD therapy must take both of these factors into account.

Source link: https://ui.adsabs.harvard.edu/abs/2013PNAS..11014995X/abstract


Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice

We find that intraventricular implantation of ganglioside GM1 leads to the phosphorylation of mutant huntingtin at certain serine amino acid residues that attenuate huntingtin toxicity and restores normal motor function in already symptomatic HD mice. Our studies have found a potential treatment for HD that emphasizes posttranslational translation of mutant huntingtin with important effects on disease pathogenesis.

Source link: https://ui.adsabs.harvard.edu/abs/2012PNAS..109.3528D/abstract


Huntington disease skeletal muscle is hyperexcitable owing to chloride and potassium channel dysfunction

Huntington disease is a progressive and fatal genetic disorder with debilitating motor and cognitive abnormalities. However, no new research has looked at the membrane properties that control contraction in Huntington disease muscle fibers. We observe key differences in ex vivo adult skeletal muscle from Huntington disease's R6/2 transgenic mouse model. Action potentials in diseased fibers are more easily triggered and long lasting than those in WT littermates' fabrics. In Huntington disease muscle, the expression of the muscle chloride channel, ClC-1, was impaired by improper splicing and a corresponding decrease in total Clcn1 mRNA.

Source link: https://ui.adsabs.harvard.edu/abs/2013PNAS..110.9160W/abstract

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions