biostudies-literatureUnknown5(1)Smith EJHuntingtin-lowering approaches that target huntingtin expression are a major focus for therapeutic intervention for Huntington's disease. When the cytosine, adenine and guanine repeat is expanded, the huntingtin pre-mRNA is alternatively processed to generate the full-length huntingtin and <i>HTT1a</i> transcripts. <i>HTT1a</i> encodes the aggregation-prone and highly pathogenic exon 1 huntingtin protein. In evaluating huntingtin-lowering approaches, understanding how the targeting strategy modulates levels of both transcripts and the huntingtin protein isoforms that they encode will be essential. Given the aggregation-propensity of exon 1 huntingtin, the impact of a given strategy on the levels and subcellular location of aggregated huntingtin will need to be determined. We have developedBrain communicationsfcad010https://www.ebi.ac.uk/biostudies/studies/S-EPMC9901570biostudies-literatureEarly detection of exon 1 huntingtin aggregation in zQ175 brains by molecular and histological approaches.PMC9901570Milton RELandles CBates GPSmith EJAst AGomez-Paredes CSchindler FSathasivam KOsborne GFMason MATaxy BAWanker EEZhang CDuan WfalseEarly detection of exon 1 huntingtin aggregation in zQ175 brains by molecular and histological approaches.Huntingtin-lowering approaches that target huntingtin expression are a major focus for therapeutic intervention for Huntington's disease. When the cytosine, adenine and guanine repeat is expanded, the huntingtin pre-mRNA is alternatively processed to generate the full-length huntingtin and <i>HTT1a</i> transcripts. <i>HTT1a</i> encodes the aggregation-prone and highly pathogenic exon 1 huntingtin protein. In evaluating huntingtin-lowering approaches, understanding how the targeting strategy modulates levels of both transcripts and the huntingtin protein isoforms that they encode will be essential. Given the aggregation-propensity of exon 1 huntingtin, the impact of a given strategy on the levels and subcellular location of aggregated huntingtin will need to be determined. We have developed2023-01-01T00:00:00Z20232025-04-04T12:56:42.175Z2025-04-04T12:56:42.175ZS-EPMC99015703675630710.1093/braincomms/fcad010