Investigate the role of OPA1 gene mutation in amyloid-beta 42 mediated neurodegeneration in Alzheimer’s Disease
Elizabeth A Borchers, Lydia C Payton, Ankita Sarkar
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder with no known cure to date. The disease is caused by the extra-cellular accumulation of amyloid-beta 42 (Aβ42) peptides, which results in neuronal death. We have developed transgenic Drosophila melanogaster (a.k.a fruit fly) model of AD where human Aβ42 peptide was misexpressed specifically in the Drosophila eye using the GAL4/UAS system. Our approach allows Aβ42 accumulation only in the differentiating photoreceptor neurons, which kills only the retinal neurons, and does not affect the reproductive ability as well as life span of flies. It allows us to use these flies to understand the molecular genetic basis of AD. One of the hallmark of AD is generation of reactive oxygen species (ROS) from mitochondria, which triggers neuronal death. My hypothesis is that OPA-1, a dynamin related GTPase, which regulate mitochondrial fusion, is involved in regulating Aβ42 mediated neurodegeneration. A fine balance between mitochondrial fission and fusion events is essential for normal mitochondrial and cellular function. Mutations of OPA1, an early stop signal produces small unstable mitochondrial proteins, which increases ROS levels in neurons. There is a strong correlation between increased ROS levels and mitochondrial fragmentation with neuronal death. I will investigate role of OPA1 in Aβ42 mediated neurodegeneration using our fly eye model. This gene is highly conserved between flies and humans. Thus, our studies will have significant bearings on understanding molecular genetic basis of AD and role of energy generating mitochondrial machinery in age related neurodegeneration.
Honors Thesis - Graduate
Primary Advisor's Department
Stander Symposium poster
"Investigate the role of OPA1 gene mutation in amyloid-beta 42 mediated neurodegeneration in Alzheimer’s Disease" (2017). Stander Symposium Posters. 914.