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

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)