Topic: Huntington's disease

Huntington's disease (HD) is a genetic neurodegenerative disease that damages primarily the striatum and leads to motor, cognitive and psychiatric symptoms. The HD striatum undergoes early specific epigenetic gene reprogramming, leading to progressive impairment of striatal neuron identity and function. Notably, genes that define striatal neuron identity are progressively down-regulated due to decreased histone acetylation (e.g. H3K27 acetylation -H3K27ac-). Additionally, developmental genes show an increase in H3K27ac, leading to their derepression. Histone acetylation is strongly connected t

Huntington's disease (HD) is an inherited, incurable neurodegenerative disease that primarily affects neurons in the striatum. In the present study, we successfully used an optimized cell model of HD [Kraskovskaya et al., 2023] to evaluate the effectiveness of the sigma 1 receptor agonist compound 3-PPP (N-n-propyl-3-(3-hydroxyphenyl)piperidine). We showed that striatal neurons obtained by direct reprogramming of dermal fibroblasts from HD patients (HD iSN) exhibit aggregates of mutant huntingtin, but the number of cells containing aggregates is less than 5% of the total. We also showed that t

Huntington's Disease (HD) is a monogenic and neurodegenerative disorder cause by an abnormal amount of CAG repeats in the exon 1 of the huntingtin gene, responsible for numerous transcriptional and cellular process dysfunctions, leading to neuronal death. HD mainly targets the medium spiny neurons of the striatum and more broadly the corticostriatal pathway, but other brain areas, such as the hippocampus, are also affected at more advanced stages of the disease. These deregulations are responsible for a triad of symtoms, consisting in cognitive and psychiatric symptoms that occur prior to the

Huntington's disease (HD) is a genetic neurodegenerative disorder, caused by CAG repeat expansion (>39) coding for poly-glutamine (polyQ) tract in the Huntingtin (HTT) gene. Although HD is late onset, it was shown to have an early neurodevelopmental component. In addition, DNA methylation was shown in adults to be an important epigenetic mechanism involved in HD. Here we sought to explore early pre-symptomatic neurodevelopmental alterations in DNA methylation using cerebral organoids from juvenile forms of isogenic HD pluripotent cells. We find wide-spread DNA demethylation in the mutant ce