Topic: mHTT-induced toxicity

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/