Regulation of androgen receptor function in neurons.

Androgen receptor (AR) is a transcription factor playing a crucial role in the acquisition of the male phenotype. AR localizes to the cytosol and upon androgen binding it dimerizes, translocates to the nucleus, and binds to specific DNA sequences (ARE) in the promoter of downstream target genes to regulate their expression. AR is expressed in muscles, prostate, and neurons. The mechanism by which AR regulates gene expression in muscles and prostate has been extensively studied from both the physiological and pathological context, revealing AR contribution to prostate cancer and the neurodegenerative disease spinal-bulbar muscular atrophy (SBMA). On the contrary, the role of AR in the regulation of neuronal function is not fully understood. Therefore, the aim of this project is to investigate the role of AR in neurons, and in particular to identify what are the AR direct downstream target genes in these cells. To this aim, I performed AR-ChIP combined with qPCR in cortical and hippocampal neurons, where AR is expressed. This study will open novel insight on the physiological role of AR in the central nervous system and will inform on the putative targets that could be manipulated to delay, if not stop, the progression of SBMA.

Androgen receptor (AR) is a transcription factor playing a crucial role in the acquisition of the male phenotype. AR localizes to the cytosol and upon androgen binding it dimerizes, translocates to the nucleus, and binds to specific DNA sequences (ARE) in the promoter of downstream target genes to regulate their expression. AR is expressed in muscles, prostate, and neurons. The mechanism by which AR regulates gene expression in muscles and prostate has been extensively studied from both the physiological and pathological context, revealing AR contribution to prostate cancer and the neurodegenerative disease spinal-bulbar muscular atrophy (SBMA). On the contrary, the role of AR in the regulation of neuronal function is not fully understood. Therefore, the aim of this project is to invistigate the role of AR in neurons, and in particular to identify what are the AR direct downstream target genes in these cells. To this aim, I performed AR-ChIP combined with qPCR in cortical and hippocampal neurons, where AR is expressed. This study will open novel insight on the physiological role of AR in the central nervous system, and will inform on the putative targets that could be manipulated to delay, if not stop, the progression of SBMA.