Stimulating Membrane Repair in Neuroblastoma Cells Compromised by APP Overexpression
Submission Type
Synchronous Poster
Area of Study or Work
Biochemistry
Zoom Meeting
Faculty Advisor
Thomas Kwiatkowski
Expected Graduation Date
2022
Start Date
4-11-2021 2:00 PM
End Date
4-11-2021 3:00 PM
Abstract
Progressive neurodegeneration is the driving force for the cognitive decline in elderly populations with Alzheimer Disease (AD). A hallmark characteristic of AD is the accumulation of amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFT) within the brain tissue, which results in neuronal death. Aβ plaques arise due to the overexpression of Amyloid Precursor Protein (APP). Under normal conditions APP serves to stabilize and protect neuronal synapses, however, in AD the APP gene is often duplicated which leads to the overexpression of APP. New unpublished findings from our collaborators at The Ohio State University has found evidence that the overexpression of APP in neuronal cells results in plasma membrane repair defects and diminished membrane integrity. Revealing a new pathophysiological mechanism that contributes to the progression of AD. This project we will test the hypothesis that activating or overexpressing specific membrane repair proteins in neurons will rescue the repair defects in APP overexpressed cells. Thus modulating the function of such repair proteins may have therapeutic benefits for AD. We will test this hypothesis through performing a repair damage assay on Neuro2a cells under three conditions. 1) Untreated control cells 2) APP overexpressed cells 3) APP and membrane repair protein overexpressed cells. To quantify membrane repair efficiency, we will measure the concentration of the intracellular lactate dehydrogenase enzyme (LDH) that leaks into the cell supernatant post damage. We expect to see a rescue in membrane repair when APP overexpressed cells also overexpress membrane repair proteins.
Stimulating Membrane Repair in Neuroblastoma Cells Compromised by APP Overexpression
Progressive neurodegeneration is the driving force for the cognitive decline in elderly populations with Alzheimer Disease (AD). A hallmark characteristic of AD is the accumulation of amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFT) within the brain tissue, which results in neuronal death. Aβ plaques arise due to the overexpression of Amyloid Precursor Protein (APP). Under normal conditions APP serves to stabilize and protect neuronal synapses, however, in AD the APP gene is often duplicated which leads to the overexpression of APP. New unpublished findings from our collaborators at The Ohio State University has found evidence that the overexpression of APP in neuronal cells results in plasma membrane repair defects and diminished membrane integrity. Revealing a new pathophysiological mechanism that contributes to the progression of AD. This project we will test the hypothesis that activating or overexpressing specific membrane repair proteins in neurons will rescue the repair defects in APP overexpressed cells. Thus modulating the function of such repair proteins may have therapeutic benefits for AD. We will test this hypothesis through performing a repair damage assay on Neuro2a cells under three conditions. 1) Untreated control cells 2) APP overexpressed cells 3) APP and membrane repair protein overexpressed cells. To quantify membrane repair efficiency, we will measure the concentration of the intracellular lactate dehydrogenase enzyme (LDH) that leaks into the cell supernatant post damage. We expect to see a rescue in membrane repair when APP overexpressed cells also overexpress membrane repair proteins.