Bottom-up design of small molecules that stimulate exon 10 skipping in mutant MAPT pre-mRNA.

ABSTRACT: One challenge in chemical biology is to develop small molecules that control cellular protein content. The amount and identity of proteins are influenced by the RNAs that encode them; thus, protein content in a cell could be affected by targeting mRNA. However, RNA has been traditionally difficult to target with small molecules. In this report, we describe controlling the protein products of the mutated microtubule-associated protein tau (MAPT) mature mRNA with a small molecule. MAPT mutations in exon 10 are associated with inherited frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17), an incurable disease that is directly caused by increased inclusion of exon 10 in MAPT mRNA. Recent studies have shown that mutations within a hairpin at the MAPT exon 10-intron juncti

SUBMITTER: Luo Y 

PROVIDER: S-EPMC4334360 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature