Elucidating the role of the innate immune complement pathway in brain development and in Autism Spectrum Disorders

• Grant number: 15/50138-4
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2016
• End date: November 30, 2018
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Agreement: Weizmann Institute of Science
• Principal Investigator: Andréa Laurato Sertié
• Grantee: Andréa Laurato Sertié
• Principal researcher abroad: Orly Reiner
• Institution abroad: Weizmann Institute of Science, Israel
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil
• Associated research grant(s): 16/50324-5 - Gene expression analysis on in vitro neuronal models and post-mortem brain tissues to understand Autism Spectrum Disorder, AP.R SPRINT

Abstract

This proposal is aimed to further characterize this important pathway in the developing brain and to understand how it is involved in ASD. The specific objectives include: 1) Further analyze and characterize the complement pathway in the developing brain using mouse models; 2) Expand and validate ASD related variants in the complement pathway; 3) Focus on specific ASD related potentially deleterious variants, generate patient-derived induced pluripotent stem cells (iPSC) lines, and subject the iPSC-derived neural stem cells and neurons to functional studies in order to unravel how complement system dysregulation may be presented as ASD. This collaborative study is likely to shed light on the involvement of a cascade that acts in the periphery as an immune surveillance system in brain development and in ASD. This new approach will increase our understanding of the developmental events that lead to ASD and may lead to future development of therapeutic agents. (AU)

Scientific publications

(4)

(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)

GOMES, ANA KAROLYNE SANTOS; DANTAS, RAFAELLY MAYARA; YOKOTA, BRUNO YUKIO; SILVA, ANDRE LUIZ TELES E; GRIESI-OLIVEIRA, KARINA; PASSOS-BUENO, MARIA RITA; SERTIE, ANDREA LAURATO. Interleukin-17a Induces Neuronal Differentiation of Induced-Pluripotent Stem Cell-Derived Neural Progenitors From Autistic and Control Subjects. FRONTIERS IN NEUROSCIENCE, v. 16, p. 10-pg., 2022-03-14. (15/50138-4)

MAGDALON, JULIANA; MANSUR, FERNANDA; TELES E SILVA, ANDRE LUIZ; DE GOES, VITOR ABREU; REINER, ORLY; SERTIE, ANDREA LAURATO. Complement System in Brain Architecture and Neurodevelopmental Disorders. FRONTIERS IN NEUROSCIENCE, v. 14, FEB 5 2020. (15/50138-4)

MANSUR, FERNANDA; TELES E SILVA, ANDRE LUIZ; SANTOS GOMES, ANA KAROLYNE; MAGDALON, JULIANA; DE SOUZA, JANAINA SENA; GRIESI-OLIVEIRA, KARINA; PASSOS-BUENO, MARIA RITA; SERTIE, ANDREA LAURATO. Complement C4 Is Reduced in iPSC-Derived Astrocytes of Autism Spectrum Disorder Subjects. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 14, JUL 2021. (15/50138-4)

SANCHEZ-SANCHEZ, SANDRA M.; MAGDALON, JULIANA; GRIESI-OLIVEIRA, KARINA; YAMAMOTO, GUILHERME L.; SANTACRUZ-PEREZ, CAROLINA; FOGO, MARIANA; PASSOS-BUENO, MARIA RITA; SERTIE, ANDREA L.. Rare RELN variants affect Reelin-DAB1 signal transduction in autism spectrum disorder. Human mutation, v. 39, n. 10, p. 1372-1383, OCT 2018. (14/25646-3, 15/50138-4)