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.
Highlights
DBDHR ligand binding domain (LBD)Deletion of the LBD domain results in a constitutively active receptor with activity similar to that seen in full length ligandbound receptor
39 Orr CR, Montie HL, Liu Y et al An interdomain interaction of the androgen receptor is required for its aggregation and toxicity in spinal and bulbar muscular atrophy
We review the role the folding of the androgen receptor (AR) plays in the pathogenesis of spinal-bulbar muscular atrophy, a neuromuscular degenerative disease arising from expansion of the polyglutamine repeat
Summary
Deletion of the LBD domain results in a constitutively active receptor with activity similar to that seen in full length ligandbound receptor. This provides evidence for the transcriptional activity of the NTD. Deletion of part or the entire domain has been reported to result in weak transcriptional activity further denoting the importance of this region to the activity of the AR protein [5]. The region of the NTD termed the AF1 mainly mediates this transactivation activity of the receptor [6]. The receptor NTD & polymorphisms in polyglutamine & polyglycine repeats Several amino acid repeat sequences are located in the NTD, with the two largest, a polyglutamine repeat (poly-Q) and a polyglycine repeat (poly-G), being highly polymorphic (Figure 1). The poly-Q tract is coded by (CAG)nCAA and spans from 9 to 36 gluta-
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
