Presenter(s)

    Catherine Yeates, Ankita Sarkar, Prajakta Deshpande

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    Description

    Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder that currently has no cure and few effective treatments. One process that underlies the pathology of AD is the accumulation of amyloid beta 42 (Aβ42) plaques, which leads to aberrant activation of cell signaling pathways and neurodegeneration. Many transgenic models use the expression of human Aβ42 throughout the entire central nervous system or developing eye. Here we use a Drosophila eye model of AD to investigate interactions between wild-type and Aβ42-expressing neurons. We have developed a two-clone system using the FLP/FRT and Gal80/Gal4/UAS approaches to generate animals with GFP-negative wild-type (WT) clones of cells adjacent to GFP-positive Aβ42-expressing clones. Surprisingly, we found that WT clones, which do not express Aβ42, are eliminated by cell death, leading to a significant decrease in clone size compared to Aβ42-expressing clones. Furthermore, the evolutionarily conserved c-Jun N-terminal kinase (JNK) signaling pathway is induced in Aβ42-expressing cells. However, it is the WT sister clones that are preferentially affected by the increase in JNK activity from Aβ42-expressing cells. Downregulating JNK signaling in the Aβ42-expressing cells restores the size of the wild-type clones. This suggests that complex crosstalk between Aβ42-expressing cells and adjacent WT cells leads to JNK-mediated neurodegeneration of WT tissue.

    Publication Date

    4-22-2020

    Project Designation

    Independent Research

    Primary Advisor

    Madhuri Kango-Singh, Amit Singh

    Primary Advisor's Department

    Biology

    Keywords

    Stander Symposium project, College of Arts and Sciences

    United Nations Sustainable Development Goals

    Good Health and Well-Being

    Activation of JNK Signaling in Aβ42-expressing Neurons Triggers Cell Death in Wild-Type Neurons in a Drosophila Eye Model of Alzheimer’s Disease

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