miR-277 ameliorates Aβ42-mediated neurodegeneration in Drosophila eye model of Alzheimer’s Disease

miR-277 ameliorates Aβ42-mediated neurodegeneration in Drosophila eye model of Alzheimer’s Disease

Authors

Presenter(s)

Prajakta Deshpande, Anuradha Chimata Venkatakrishnan; other authors: Chao-Yi Chen, Catherine Yeates, Chun-Hong Chen, Madhuri Kango-Singh, Amit Singh

Comments

Presentation: 10:40-11:00 a.m., Science Center 150

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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. We misexpressed human Aβ42 in the developing retina of Drosophila, which 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 (miRNAs) which post-transcriptionally regulate expression of genes by degrading mRNA of the target genes. In a forward genetic screen with candidate 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. Here we provide a mechanism of how miR-277 modulates Aβ42-mediated neurodegeneration and demonstrate its neuroprotective role in Aβ42-mediated neuropathology.

Publication Date

4-19-2023

Project Designation

Graduate Research

Primary Advisor

Amit Singh, Madhuri Kango-Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium, College of Arts and Sciences

miR-277 ameliorates Aβ42-mediated neurodegeneration in Drosophila eye model of Alzheimer’s Disease

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