Topic: mutant huntingtin

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

The aberrant formation and accumulation of the misfolded polyglutamine （polyQ） containing proteins in the nuclei are considered to be the major hallmark and cause of many neurodegenerative diseases, including Spinocerebellar ataxias （SCAs）, Huntington Disease （HD）, Spinal and Bulbar Muscular Atrophy （SBMA）, and Dentatorubro pallidoluysian atrophy （DRPLA）. It is, therefore, believed that intervening biosynthesis, resolution, and clearance of the misfolded proteins, may represent potential therapeutic approaches. Previous studies have found that the BFRF1 protein of the Epstein-Barr virus （EBV）

Huntington’s disease (HD) is a devastating neurodegenerative disease resulting from a CAG/ polyglutamine expansion in Huntingtin (HTT), with no disease-modifying treatment. Current gene therapies targeting the mutant huntingtin (mHTT) have faced challenges, which have prompted continued interest in small molecules as potential therapeutic agents. We focused on a set of small molecules that selectively bind to sigma 2 receptor (σ2R), which was identified recently as the transmembrane protein 97 (σ2R/TMEM97) and located in the endoplasmic reticulum. Although the exact biological function of σ2R/