mir-277 Targets Hid to Ameliorate Aβ42-mediated Neurodegeneration in Drosophila Eye Model of Alzheimer’s Disease

Title

mir-277 Targets Hid to Ameliorate Aβ42-mediated Neurodegeneration in Drosophila Eye Model of Alzheimer’s Disease

Authors

Presenter(s)

Prajakta D. Deshpande

Files

Description

Alzheimer’s disease (AD), an age-related progressive neurodegenerative disorder, exhibits reduced cognitive functions with no cure to date. One of the reasons for AD is the extracellular accumulation of Amyloid-beta 42 (Aβ42) plaques. Misexpression of human Aβ42 in the developing retina of Drosophila exhibits AD-like neuropathology. Accumulation of Aβ42 plaque(s) triggers aberrant signaling resulting in neuronal cell death by unknown mechanism(s). We screened for microRNAs which post-transcriptionally regulate expression of genes by degrading mRNA of the target genes. In a forward genetic screen using miRNAs, we identified mir-277 as a genetic modifier of Aβ42-mediated neurodegeneration. Gain-of-function of mir-277 rescues Aβ42 mediated neurodegeneration whereas loss-of-function of mir-277 enhances Aβ42 mediated neurodegeneration. Moreover, misexpression of higher levels of mir-277 in the GMR>Aβ42 background restores the retinal axonal targeting indicating functional rescue. Furthermore, we have identified head involution defective (hid) as one of the targets of mir-277 by Fly TargetScan and validated by luciferase assay and qPCR. The hid transcript levels are decreased by one third when mir-277 is misexpressed in the GMR>Aβ42 background in comparison to the GMR>Aβ42 fly model. Here we provide a mechanism of how mir-277 modulates Aβ42-mediated neurodegeneration by regulating hid transcript levels and demonstrate its neuroprotective role in Aβ42-mediated neuropathology.

Publication Date

4-22-2021

Project Designation

Graduate Research

Primary Advisor

Madhuri Kango-Singh, Amit Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium Posters, College of Arts and Sciences

United Nations Sustainable Development Goals

Good Health and Well-Being

mir-277 Targets Hid to Ameliorate Aβ42-mediated Neurodegeneration in Drosophila Eye Model of Alzheimer’s Disease

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