Involvement of O-GlcNAcylation in astrocyte activation during development of experimental autoimmune encephalomyelitis

• Grant number: 19/25305-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2020
• End date: February 28, 2021
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Thiago Mattar Cunha
• Grantee: Larissa Pinto de Andrade
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Astrocytes are the most abundant glial cells in the central nervous system (CNS) and are responsible for the energy supply of neurons. In situations of CNS disorders, besides inducing inflammatory response by the release of cytokines and chemokines, they are also able to alter their metabolism to maintain cerebral homeostasis. O-Glycosyl Transferase (OGT) is an enzyme of the hexamine pathway - a branch of the glycolytic pathway - responsible for the O-GlcNAcylation process, which consists of the addition of the UDP-N-acetyl glucosamine group (pathway final product) to hydroxyls of serine/threonine’s target proteins. Literature data suggest that O-GlcNAcylation is associated from inflammatory responses generated by immune cells to the development of neurodegenerative diseases. Previous laboratory data show that OGT is widely expressed in astrocytes. Knowing the relevance of this cell subtype in the development of neurodegenerative processes, such as EAE (Experimental Autoimmune Encephalomyelitis), we aim to investigate the role of OGT in astrocyte activation in vitro, under inflammatory stimuli, and in vivo in the neuroinflammation model (EAE). (AU)