SCIENTIFIC POSTER
Targeted protein degradation of mutant Huntingtin aggregates: in vitro assays and tools to support development of mHTT-Targeting PROTACs
Since Huntington’s disease (HD) is caused by expression of mutant huntingtin (mHTT) protein, lowering expression of mHTT is a key therapeutic strategy for HD. Reducing the amount of mHTT protein in HD-affected brains is predicted to prevent cellular dysfunction, neurodegeneration and alleviate symptoms of the disease. To date, HTT-lowering approaches include antisense oligonucleotides and RNA interference targeting mRNA, and zinc finger transcriptional repressors and CRISPR-Cas9 methods by targeting DNA. Alternative modalities to enhance protein clearance pathways e.g. the autophagy-lysosome pathway and the ubiquitinproteasome system (UPS) are under investigation.
PROteolysis TArgeting Chimera (PROTAC)-based approaches utilize heterobifunctional molecules to simultaneously bind both the target and an ubiquitin E3 ligase to promote the ubiquitination and degradation of the target molecule.
Recently presented at the Society for Neuroscience 2019 conference in Chicago by our expert, Elizabeth van der Kam, download your copy of this scientific poster now and discover more.