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Dysregulation of integrated stress response (ISR) pathway in Fragile X syndrome and autism

Project Overview

Mr. Hooshmandi’s research will examine the hypothesis that reduced phosphorylation of eIF2α excessively stimulates general translation in Fmr1 KO mice during brain development, contributing to the pathophysiology of Fragile X syndrome (FXS) and potentially of other forms of autism. They propose three main aims in this study as follows: (1) to measure p-eIF2α at different time points during early postnatal brain development in ASD mouse models and in patient lymphocytes, (2) to investigate the mechanisms by which aberrant eIF2α affects brain development and leads to abnormal neuronal function,(3) to investigate the role of hypo-phosphorylated eIF2α in mediating abnormal cellular and behavioral phenotypes in a mouse model of FXS. The proposed research could provide the autism research community with a novel biomarker (p-eIF2α) in forms of autism with altered global protein synthesis, as well as a new potential therapeutic avenue involving compounds targeting p-eIF2α.

Principal Investigator

Mehdi Hooshmandi , McGill University

Partners and Donors

McGill University

Project Ongoing

Dysregulation of integrated stress response (ISR) pathway in Fragile X syndrome and autism

  • Grant Type

    Capacity building grants

  • Area of research

    Neurodevelopment

  • Disease Area

    Autism

  • Competition

    Brain Canada - Kids Brain Health Network Training Awards

  • Province

    Québec

  • Start Date

    2018

  • Total Grant Amount

    $70,000

  • Health Canada Contribution

    $35,000