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Dynamic palmitoylation regulates TDP-43 nucleocytoplasmic transport in ALS

Aperçu du projet

Common features in amyotrophic lateral sclerosis (ALS) include misdirected proteins that build up over time and lead to large protein clumps that are toxic to the cell and lead to cell death. In ALS, special cells known as motor neurons are particularly affected. These neurons have very long extensions known as axons that connect the brain and spinal cord to our muscles. Axons can be meters long. Consequently, proteins must travel long distances along axons to mediate their effects, like metabolism or signaling muscles to move. The first step in ALS involves proteins being directed to the wrong part of the cell. This can cause proteins to perform their functions in the wrong place. Alternatively, these misdirected proteins cannot be removed by the cell and they build-up and form large clumps composed of the mislocalized proteins and other critical cellular components. Our lab has identified a process that regulates this protein localization, known as fatty acylation. Fatty acylation involves the addition of a fat to proteins. The fat acts like a postal code to direct proteins to the proper location in the cell and helping them to stick there. Fatty acylation is reversible, which allows proteins to be re-directed within the cell multiple times. It also makes it a more druggable target. We have identified key proteins involved in ALS that undergo acylation. We think acylation may deliver these proteins to the wrong areas in the cell and this may be a common feature in ALS. By identifying the proteins that regulate this process, we hope this will contribute to the design of new therapeutic targets in ALS.

Chef d'équipe

Dale Martin , University of Waterloo

Partenaire et Donateurs

ALS Society of Canada

Projet en cours

Dynamic palmitoylation regulates TDP-43 nucleocytoplasmic transport in ALS

  • Type de subvention

    Team grants

  • Domaine de recherche

    Neurodegeneration

  • Disease Area

  • Compétition

    Société canadienne de la SLA - Fondation Brain Canada - Bourses de découverte

  • Province

    Québec

  • Date de Début

    2024

  • Montant total du financement

    $125,000