Role of Dpp signaling pathway in promoting survival of retinal neurons in Aβ42 mediated neurodegeneration

Role of Dpp signaling pathway in promoting survival of retinal neurons in Aβ42 mediated neurodegeneration

Presenter(s)

Neha Gogia, Jason N Kleppel, Ankita Sarkar

Description

Alzheimer's disease is a progressive neurodegenerative disorder with no known cure to date. One cause of Alzheimer's neuropathy is the generation of Amyloid-beta-42 (Aβ42) aggregates that trigger cell death by unknown mechanisms. Using a transgenic Drosophila eye model misexpressing human Aβ42, we observed the AD-like neuropathy. In a forward genetic screen we have identified Decapentaplegic (Dpp), a morphogen, as one of the genetic modifiers of Aβ42 mediated neurodegeneration. Dpp acts as the ligand for the Dpp pathway, which exhibits suppression of retinal neuron’s cell death. The Dpp signaling pathway involves several key components. We examined the Dpp signaling pathway and its members in modifying Aβ42 mediated neuropathy. We have demonstrated that upregulating Dpp signaling pathway, by misexpressing Dpp (using UAS dpp) and Thickveins (using UAS tkv) can rescue Aβ42 mediated neurodegeneration. The number of dying cells marked with TUNEL staining was also reduced and the axonal targeting was restored from the retina to the brain, which was marked by 24B10 staining. We will test the role of Dpp signaling in Aβ42 plaques mediated neurodegeneration. Furthermore, we will analyze, if these modifiers act independent and/or parallel of each other or whether they have a linear relationship in triggering neurodegenerative response due to accumulation of Aβ42. The results from our studies will be presented.

Publication Date

4-5-2017

Project Designation

Honors Thesis - Graduate

Primary Advisor

Amit Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium project

Role of Dpp signaling pathway in promoting survival of retinal neurons in Aβ42 mediated neurodegeneration

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