Project Overview
“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.”
Partners and Donors
Huntington Society of Canada
