We previously developed a class of degradation-inducing agents targeting the β-sheet-rich structure typical of such aggregates, and we showed that these agents dose-, time-, and proteasome-dependently decrease the intracellular level of mutant huntingtin with an extended polyglutamine tract, which correlates well with the severity of Huntington's disease.
Hence, the expression of the normal HTT gene may take part in the steroidogenic events in aforementioned organs in the physiological state, whereas the mutant HTT gene may cause defects in steroidogenesis in HD.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the gene encoding the huntingtin (Htt) protein, which results in a protein containing an abnormally expanded polyglutamine (polyQ) sequence.
Since increased melatonin could have global beneficial effects on brain function, we suggest that the increased melatonin measured in presymptomatic HD sheep is part of an autoprotective response to mutant huntingtin toxicity that may account, at least in part, for the late onset of disease that characterises HD.
Here we describe the first ultrasensitive sandwich immunoassay that quantifies HTT phosphorylated at residue S13 and demonstrate its utility for specific analyte detection in preclinical models of HD.
Suppressing HTT production with antisense oligonucleotides (ASOs) is a promising treatment strategy for HD; however, the difficulty of delivering ASOs to deep brain structures is a major barrier for its clinical application.
The present results are in line with the results obtained in our previous studies with isolated brain mitochondria and cultured striatal neurons from YAC128 and R6/2 mice, in which we demonstrated that mutant huntingtin at early stages of HD pathology does not deteriorate mitochondrial functions.
To test this hypothesis, primary cultures of either hippocampal or striatal neurons were prepared from either wild-type mice or a knock-in HD mouse model which contains 140 poly-glutamine repeats in the huntingtin protein (htt<sup>Q140/Q140</sup>).
Here, we examine the tolerability and efficacy of non-selective HTT lowering with an AAV5 encoded miRNA targeting human HTT (AAV5-miHTT) in the humanized Hu128/21 mouse model of HD.
We tested this hypothesis in the scenario of Huntington disease (HD), a neurodegenerative disorder that is caused by the mutant HTT (mHTT) protein with an expanded polyglutamine (polyQ) stretch.
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a trinucleotide repeat expansion in the huntingtin (HTT) gene, which is expressed ubiquitously throughout the brain and peripheral tissues.
In CSF of HTT gene expansion carriers, we found increased levels of proinflammatory cytokines, including IL-17, and increased consumption of the lymphocyte growth factor IL-7 before motor onset of HD.
Huntington's disease (HD) is a neurodegenerative late-onset genetic disorder caused by CAG expansions in the coding region of the Huntingtin (HTT) gene, resulting in a poly-glutamine (polyQ) expanded HTT protein.
Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by CAG triplet repeats expansion in exon 1 of the Huntingtin gene (<i>HTT</i>).
To better understand the time-course of synaptic plasticity deficits in HD, as well as the impact of heterozygous and homozygous huntingtin mutations, we quantified basal synaptic connectivity, presynaptic release probability, presynaptically mediated post-tetanic potentiation (PTP) and postsynaptically mediated LTP at presymptomatic, early symptomatic and late symptomatic ages in heterozygous and homozygous Q175FDN knock-in HD mice.