Trinucleotide Repeats and Protein Folding and Disease: the Perspective From Studies With the Androgen Receptor

Abstract

The androgen receptor (AR), a ligand activated transcription factor plays a number of roles in reproduction, homeostasis and pathogenesis of disease. It has two major polymorphic sequences; a polyglutamine and a polyglycine repeat that determine the length of the protein and influence receptor folding, structure and function. Here, we review the role the folding of the AR plays in the pathogenesis of spinal-bulbar muscular atrophy (SBMA), a neuromuscular degenerative disease arising from expansion of the polyglutamine repeat. We discuss current management for SBMA patients and how research on AR structure function may lead to future drug treatments.

Financial & competing interests disclosure

Research in the McEwan laboratory is supported by Prostate Cancer UK, BBSRC, Chief Scientist's Office of the Scottish Government (Project Grant ETM/258) and IOMET Pharma. FAO is supported by a studentship from Prostate Cancer UK (S10–10). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Research in the McEwan laboratory is supported by Prostate Cancer UK, BBSRC, Chief Scientist's Office of the Scottish Government (Project Grant ETM/258) and IOMET Pharma. FAO is supported by a studentship from Prostate Cancer UK (S10–10). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.