Anti-inflammatory effect of the P2X7 receptor antagonist, brilliant blue g, and its impact on cell therapy in an animal model of Parkinson's Disease

• Grant number: 17/24400-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2018
• Effective date (End): December 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Alexander Henning Ulrich
• Grantee: Carolina de Moura Albino
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Parkinson's disease (PD) is a chronic and progressive degenerative disease of the central nervous system, characterized by the death of dopaminergic neurons in the substantia nigra and striatum. Literature data suggests that the purinergic P2X7 receptor exerts pro-inflammatory effects in PD pathophysiology, estimating cytokines secretion by active microglia, resulting in a neuronal loss by pyroptose and contributing to the worsening of the disease. Previous data from our laboratory showed that P2X7 receptor antagonist Brilliant Blue G (BBG) reverts dopaminergic deficit observed in the 6-hydroxydopamine (6-OHDA) animal model of PD. The mainly hypothesis regarding this effect is due to the attenuation of inflammatory process. Thus, one aim of this project is to evaluate inflammatory modulation of BBG treatment in the 6-OHDA animal model of PD through biochemical and in vitro assays. Moreover, taking into account that cell transplantation is one of the most studied treatments for neurodegenerative diseases nowadays, and that survival and integration of transplanted cells is challenging, this project proposes inflammatory modulation with BBG treatment prior to cell transplantation, evaluating the efficacy of cell insertion and survival, and reversal of dopaminergic deficit in the animal model of PD. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

OLIVEIRA-GIACOMELLI, AGATHA; ALBINO, CAROLINA M.; NOBREGA DE SOUZA, HELLIO DANNY; CORREA-VELLOSO, JULIANA; DE JESUS SANTOS, ANA PAULA; BARANOVA, JULIANA; ULRICH, HENNING. P2Y6 and P2X7 Receptor Antagonism Exerts Neuroprotective/ Neuroregenerative Effects in an Animal Model of Parkinson's Disease. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 13, NOV 8 2019. (12/50880-4, 18/07366-4, 17/24400-9)