Wingless, a mediator of crosstalk between Amyloid-beta 42 expressing and wild-type neurons in Alzheimer’s disease

Title

Wingless, a mediator of crosstalk between Amyloid-beta 42 expressing and wild-type neurons in Alzheimer’s disease

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Description

Alzheimer’s disease (AD), a common form of dementia and an age related progressive neurodegenerative disorder, manifests as memory loss and reduced cognitive ability. One of the hallmarks of AD is formation of the Amyloid-beta 42 (hereafter Aβ42) plaques, which triggers oxidative stress due to aberrant signaling and finally results in the death of neurons. However, the exact mechanism causing cell death is still not well understood. We misexpressed high levels of human Aβ42 protein in the developing fly retina, which mimics AD like neuropathology. In a forward genetic screen, we identified members of highly conserved Wingless (Wg) signaling pathway as modifiers of the Aβ42 mediated neurodegeneration. Misexpression of negative regulator of Wg like Shaggy kinase (sgg) or a dominant negative form of Drosophila T-cell factor (dTCFDN5) or blocking Wg transport specifically by downregulating Porcupine (using porcupineRNAi) rescued Aβ42 mediated neurodegeneration by reducing the number of dying cells and restoring the axonal targeting from the retina to the brain. It is also known that Wg induces cell death in the early eye developmental stage of Drosophila. We therefore want to understand by what mechanism and in which cells the Wg signaling is triggering cell death, whether it’s the Aβ42 misexpressing cells or the neighboring wild type cells. In order to approach this question we have developed a two clone system in our lab to understand the crosstalk between the two cell populations, where we have shown that the wild type neighboring cells are undergoing cell death compared to the Aβ42 misexpressed cells.

Publication Date

4-18-2018

Project Designation

Graduate Research

Primary Advisor

Madhuri Kango-Singh, Amit Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium poster

Comments

Presenter: Ankita Sarkar

Wingless, a mediator of crosstalk between Amyloid-beta 42 expressing and wild-type neurons in Alzheimer’s disease

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