Degeneration and development of the nervous system: the role of epigenetic processes

Abstract

The complexity of the nervous system materializes both in its formation during development and in processes related to neurodegeneration. Relevant factors in both degeneration and development are those related to epigenetic regulation. In fact, epigenetic regulation seems to be important for tissue response in neurodegenerative processes, including the initial inflammatory response. On the other hand, during development, the availability of genetic information through mechanisms that include microRNA regulation, another process of epigenetic regulation, seems to be fundamental for determining neuronal differentiation. In this project, we are interested in determining aspects related to epigenetic regulation in degeneration and development of the nervous system. Specifically, we intend to evaluate the role of the enzyme EZH2 during spinal cord neurodegeneration after mechanical trauma, as well as argonaute protein 2 (AGO2) in the neuronal differentiation that occurs during retinal development. For this, we will employ molecular and cellular biology techniques. It should be noted that our group masters the proposed methodologies, notably those related to our internships held at research or technological development institutions, such as University of Florida (2011), Plexon Neurotechnology (2011) and Cold Spring Harbor (2012). Our goal is to determine whether control of the activity and expression of the enzyme EZH2 could become a therapeutic target for the treatment of spinal cord injury, as well as AGO2 for degenerative retinal diseases that mainly affect specific neuronal subtypes, such as rods in retinitis pigmentosa, cones in age-related macular degeneration and ganglion cells in glaucoma. This proposal is supported by Dra. Jean X. Jiang (Harvard University / University of Texas Health Science Center, USA), Stephanie M. Willerth (University of Victoria, Canada), Florence E. Perrin (University of Montpellier, France), Sten Rüdiger (Humboldt University, Germany) and other research groups based at the University of São Paulo, UFMG and INPE, as well as postdoctoral students, and graduate and undergraduate students engaged with this proposal. It is important to highlight that the support given to this proposal will be essential for the continuity of projects linked to the FAPESP postdoctoral fellowships (17/ 18977-1), doctorate (16/17329-3), master's degree (17/26388-6, 18/06316-3 and 18/23775-1) and scientific initiation (18/19300-8). Finally, it should be stressed that several research groups from our institution will benefit with this proposal, since UFABC research laboratories are multi-user facilities. (AU)