Study of the inflammatory mechanisms mediated by innate immunity receptors in Amyotrophic Lateral Sclerosis

• Grant number: 15/10892-1
• Support type: Regular Research Grants
• Duration: June 01, 2016 - November 30, 2018
• Field of knowledge: Biological Sciences - Morphology
• Principal Investigator: Renato Barboza
• Grantee: Renato Barboza
• Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Assoc. researchers: Daniel Carneiro Carrettiero ; Karina Ramalho Bortoluci ; Merari de Fátima Ramires Ferrari

Abstract

Activation of innate immunity receptors, such as Toll-like receptors (TLRs) and NOD-like receptors (NLR), in neurons, induces inflammatory processes that contribute to the development of neurodegenerative diseases, such as Amyotrophic lateral sclerosis (ALS). For that reason, the knowledge of the function of these receptors, as well as the comprehension of their activation processes are fundamental for understanding the immune modulatory mechanism that lead to neurodegeneration. In view of this, the objective of this project is to study the inflammatory pathways induced by the activation of TLR and NLR correlated with the course of neurodegenerative diseases. For this, it will be used a murine model of ALS using a SOD1 mutant transgenic mice (G93A); neuron cultures derived from human neural cell line (SH-SY5Y) that overexpress the protein hSOD1G93A; as well as BV-2 cell cultures (murine microglia). After the establishment of these models, we will analyze the expression and the signaling pathway of TLR2, 3, and 4. To study the influence of NLR we will first analyze the inflammasome complex formation and the production of IL-1 and Caspase-1 bioactive forms. We will also evaluate the production of inflammatory mediators induced by these receptors. With these results, it is expected to understand the inflammatory mechanisms involved in the neurodegenerative processes. The knowledge acquired herein may provide a basis for proposing intervention studies related with the development of the neurodegenerative diseases. (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)

BARBOZA, RENATO; HASENKAMP, LUTERO; BARATEIRO, ANDRE; MURILLO, OSCAR; MACHADO PEIXOTO, ERIKA PAULA; LIMA, FLAVIA AFONSO; REIS, ARAMYS SILVA; GONCALVES, LIGIA ANTUNES; EPIPHANIO, SABRINA; MARINHO, CLAUDIO R. F. Fetal-Derived MyD88 Signaling Contributes to Poor Pregnancy Outcomes During Gestational Malaria. FRONTIERS IN MICROBIOLOGY, v. 10, JAN 29 2019. Web of Science Citations: 1.