miR-277 targets hid to ameliorate Aβ42-mediated neurodegeneration in Drosophila eye model of Alzheimer’s Disease
Presenter(s)
Anuradha Venkatakrishnan, 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. 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. 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 ̴2.3-fold when miR-277 is misexpressed in the GMR>Aβ42 background in comparison to the GMR>Aβ42 fly model. Hence, 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
4-20-2022
Project Designation
Graduate 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
Recommended Citation
"miR-277 targets hid to ameliorate Aβ42-mediated neurodegeneration in Drosophila eye model of Alzheimer’s Disease" (2022). Stander Symposium Projects. 2431.
https://ecommons.udayton.edu/stander_posters/2431
Comments
Presentation: 11:00 a.m.-11:20 a.m., Kennedy Union 311
Additional authors and advisors:
Prajakta Deshpande1, Chao-Yi Chen2, Anuradha Venkatakrishnan Chimata1, Catherine Yeates1, Chun-Hong Chen2,3, Madhuri Kango-Singh1,4,5,6, Amit Singh1,4,5,6,7
1. Department of Biology, University of Dayton, Dayton, OH
2. Institution of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan
3. National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan
4. Premedical Program, University of Dayton, Dayton, OH
5. Center for Tissue Regeneration & Engineering (TREND), University of Dayton, Dayton, OH
6. Integrative Science and Engineering (ISE), University of Dayton, Dayton, OH
7. Center for Genomic Advocacy (TCGA), Indiana State University, Terre Haute, IN.