One gene, many proteins: investigating the role of AR isoform 2 as a therapeutic target for SBMA
Summary: The activity of steroid hormone receptors, such as progesterone and oestrogen receptors, is modulated by a number of isoforms and splice variants in a tissue-specific manner, in both health and disease. Androgen receptor may be no exception. AR isoform 2, or AR45 by the molecular weight of its encoded widely-expressed protein, is the only naturally occurring AR isoform, arising from use of an alternative transcriptional start site in intron 1 of the AR gene and containing a short, unique seven amino-acid-long N-terminal stretch instead of the long N-terminal domain found in the full length AR. Overarching aim of this proposal is to unravel the contribution of AR isoform 2 to SBMA pathogenesis and provide a novel therapeutic target for this disease, suitable for oligonucleotide antisense targeting without running the risks associated with silencing of the only available copy of the AR gene in males.
