The Effect of Improved MG53 Proteins on Neuronal Membranes to Reduce Neuron Cell Death in a Model of Alzheimer's Disease
Loading...
Date
2024-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
The Ohio State University
Abstract
As the most prevalent cause for dementia and ultimately loss of cognitive function in middle aged to elderly individuals, Alzheimer’s disease (AD) directly impacts close to 50 million people in the United States healthcare system. AD severely impacts a person's ability to thrive by impairing memory and cognitive function, and often results in premature death. Previous work in the laboratory linked compromised plasma membranes in neurons with the progression of AD. Plasma membrane repair is a conserved process found in many different cell types that can restore the integrity of the cell membrane and prevent cellular apoptosis from injuries that would otherwise destroy the cell. Therefore, this study will build on these results not by examining the mechanisms and causes of AD, but rather by exploring the effect that membrane repair methods may have on disease progression as a possible way of developing a therapeutic approach to treat AD. The overarching aim of this study is to improve the status of AD or slow the progression of AD once the disease has already manifested and progressed.
Other results from our laboratory group show that recombinant protein MG53 (rhMG53) accelerates the process of plasma membrane repair in striated muscle cells and in neuronal cell types. MG53 localizes areas of membrane injury. In AD, amyloid-β protein aggregates cause damage to the membrane which threatens its integrity. This study aims to test whether improved versions of rhMG53, the 89A-FL (myoTRIM) and forced dimer (f-dimer) constructs, can increase repair of neuronal membranes, which could reduce the death of neurons and slow the progression of neuronal degeneration. AD cell models were created by transfecting N2a cells with wildtype MG53, 89A-FL or f-dimer plasmids in the presence of recombinant amyloid-β protein. Cells were then injured using a laser injury assay to simulate membrane damage associated with AD. A control cell model transfected with an eGFP control plasmid was utilized alongside the transfected cell models. This control plasmid was also treated with recombinant amyloid-β. Results show that expression of 89A-FL or f-dimer protein increases membrane repair to comparable levels of the expression of the wildtype MG53 protein. Future directions will aim to test efficacy of recombinant protein repair of damaged neuronal cell membranes when placed directly in complete media surrounding cell cultures as an alternative to transfection.
Description
Department of Physiology and Cell Biology Research Day Outstanding Undergraduate Poster Award
Keywords
Alzheimer's, Membrane Repair, neurons, laser injury