miR-let-7a-2, miR103a-2 and CREB1-TF as therapeutic targets to regulate the transcription of DISC1 and PDE4D in the transcriptional regulation pathway by DISC1/ATF4 complex

Abstract

Disrupted In Schizophrenia 1 (DISC1) is considered a multifunctional protein implicated in various signaling pathways with neurological relevant outcomes, with the Disrupted In Schizophrenia 1/Activating Transcription Factor 4 (DISC1/ATF4) transcriptional regulation pathway being a pathway of interest since it regulates Phosphodiesterase 4D (PDE4D) transcription. Alterations in the transcription levels of DISC1 and PDE4D have been implicated in neurodegenerative processes and the identification of therapeutic targets that regulate these processes can be of great help to promote neuroprotective processes. By using a System Biology approach, we created a mathematical model of the transcriptional regulation of the DISC1/ATF4 pathway and using this model we conducted in-silico experiments to identify potential therapeutic targets with robust control on the network. As a result, miR-let-7a-2 is reported as a transcriptional regulator of DISC1 as well as miR103-a2 and CREB1-TF as transcriptional regulators of the PDE4D. These three regulators are identified as in-silico therapeutic targets to promote neuroprotective processes against neurodegenerative mental disorders.