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Evaluating DLK activity in brain samples from Huntington’s disease patients

Aperçu du projet

« Background:Within the realm of neurodegenerative diseases, there is still a lack of effective disease-modifying treatments. Huntington’s Disease (HD) is no less immune to this issue, with only symptomatic treatment options being available for patients. In other neurodegenerative diseases, a Dual Leucine Zipper Kinase (DLK) has been identified as a novel therapeutic target and the possibility of inhibiting DLK as a potential treatment strategy is currently being addressed by a Huntington Society of Canada funded grant to the Sanders, Alpaugh, and Martin labs. To extend on this grant, I propose to evaluate the levels of DLK pro-degenerative pathway activation in human tissue samples.
Project Plan:My specific role in the Alpaugh lab this summer will be investigating the levels of DLK pro-degenerative pathway activation across Grades 1-4 by immunoblotting for total and phosphorylated levels of cJUN and its direct upstream activators MKK4 and JNK2/3. Specifically, we have already obtained cortical and putamen tissue samples from male and female HD patients (n=14 and n=7, respectively) from the University of Washington. These samples include 4 from Grade 1 (3 female, 1 male), 7 from Grade 2 (5 male, 2 female), 7 from Grade 3 (2 female, 5 male), and 3 from Grade 4 (2 female, 1 male). In addition, we will also evaluate samples from individuals without neurological disease (male: n=13, female: n=11) as a reference and samples from patients with AD as a positive control (male: n=9, female: n=5), I will process these samples, run the western blots and complete the analysis of protein expression levels. Finally, I will correlate the expression levels with clinical details (age, score on MMSE and CASI) to understand if activation of the DLK pro-degenerative pathway tracks with clinical outcomes. By the end of the summer, I expect that we will have obtained evidence about the activation of DLK in HD and how it relates to clinical outcomes, findings which will greatly compliment the ongoing preclinical studies. »

Chef d'équipe

Christiana Lammers , University of Guelph

Partenaire et Donateurs

Huntington Society of Canada

Projet en cours

Evaluating DLK activity in brain samples from Huntington’s disease patients

  • Domaine de recherche

    Neurodegeneration

  • Disease Area

    Other

  • Compétition

    Huntington Society of Canada - Brain Canada Undergraduate Student Fellowship

  • Province

    Ontario

  • Date de Début

    2025

  • Montant total du financement

    $5,000