Mediator complex in neurological disease

Abstract

Neurological diseases, including traumatic brain injuries, stroke (haemorrhagic and ischemic), and inherent neurodegenerative diseases cause acquired disability in humans, representing a leading cause of death worldwide. The Mediator complex (MED) is a large, evolutionarily conserved multiprotein that facilities the interaction between transcription factors and RNA Polymerase II in eukaryotes. Some MED subunits have been found altered in the brain, although their specific functions in neurodegenerative diseases are not fully understood. Mutations in MED subunits were associated with a wide range of genetic diseases for MED12, MED13, MED13L, MED20, MED23, MED25, and CDK8 genes. In addition, MED12 and MED23 were deregulated in the Alzheimer's Disease. Interestingly, most of the genomic mutations have been found in the subunits of the kinase module. To date, there is only one evidence on MED1 involvement in post-stroke cognitive deficits. Although the underlying neurodegenerative disorders may be different, we are confident that the signal cascades of the biological-cognitive mechanisms of brain adaptation, which begin after brain deterioration, may also differ. Here, we analysed relevant studies in English published up to June 2023. They were identified through a search of electronic databases including PubMed, Medline, EMBASE and Scopus, including search terms such as "Mediator complex", "neurological disease", "brains". Thematic content analysis was conducted to collect and summarize all studies demonstrating MED alteration to understand the role of this central transcriptional regulatory complex in the brain. Improved and deeper knowledge of the regulatory mechanisms in neurological diseases can increase the ability of physicians to predict onset and progression, thereby improving diagnostic care and providing appropriate treatment decisions.

Keywords: Brain; Mediator complex; Neurological diseases; Personalized medicine; Stroke.