Functional consequences of EZH2 epigenetical regulation on neurodegeneration and locomotor recovery after spinal cord compression

Abstract

Spinal cord injury (SCI) is a traumatic neurologic disorder with great clinical relevance due to the disruption of neuronal communication between the central nervous system and other systems of the body. Also, this interruption could aggravate by local tissue inflammation, and damage spread during injury progression. Nowadays, it is already known that epigenetic-related processes contribute to this evolution of central nervous system damage. Epigenetic is often related to alterations in the chromatin structure which are capable to change the genetic expression without altering the DNA sequence and are mainly related to histones modifications. There are primarily two histone alterations regulated for different protein complexes described: methylation, and acetylation. Histone acetylation is coordinated by the enzyme histone acetyltransferase (HAT) and on SCI is correlated with tissue regeneration. However, histones methylation which is mainly produced by enhancer of zeste homolog 2 (EZH2) is not well described in nervous system injury. Focusing on that, the aim of this project is to describe the role of EZH2 on injury progression and tissue regeneration through pharmacology inhibition (GSK343), molecular biology assays and behavior tests such as western blotting (WB), immunofluorescence (IF), TUNEL and BBB test.