Investigation of Neurodegenerative Disease-related Cofilin-Actin Rod Dynamics Using a Novel Optogenetic Approach
Author
Roberts, Davis Keith
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This item will be available on: 2024-12-01
Abstract
The presence of actin-cofilin rods in neurons is a common feature of a multitude of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Huntingtin’s disease (Bamburg, et al 2010). These rods form under oxidative and energetic stress conditions such as ATP depletion, glutamate excitotoxicity, or a highly oxidative environment, and ultimately lead to synapse loss. These stress conditions shift the equilibrium of actin, an ATP binding protein, to a primarily ADP-bound state. In our lab, we have created a light activated switch (‘CofActor’) for monitoring cofilin-actin rod formation in living cells. This allows real-time monitoring of cofilin-actin interactions in cells undergoing applied energetic or oxidative stress. In previous work, we used the CofActor system to monitor these interactions over short time scales (10 – 20 minutes). In this work, we investigate whether we can use the CofActor system to monitor cofilin-actin interactions over longer time periods (3 – 4 hours). We specifically asked whether the rounded cofilin-actin clusters formed over the short time scale could eventually transition into linear cofilin-actin rods. We used fluorescence microscopy to monitor the CofActor system expressed in HeLa cells under energetic stress (ATP-depleted) conditions induced with a cocktail of Sodium Azide (NaN3) and 2-deoxy-D-glucose (2-DG). Our findings demonstrate that cofilin-actin clusters can transition to linear cofilin-actin rods and that they provide a unique way to assess the dynamics of cofilin-actin rod formation in living cells.
Date
2023-12-15
Citation:
APA:
Roberts, Davis Keith.
(December 2023).
Investigation of Neurodegenerative Disease-related Cofilin-Actin Rod Dynamics Using a Novel Optogenetic Approach
(Honors Thesis, East Carolina University). Retrieved from the Scholarship.
(http://hdl.handle.net/10342/13302.)
MLA:
Roberts, Davis Keith.
Investigation of Neurodegenerative Disease-related Cofilin-Actin Rod Dynamics Using a Novel Optogenetic Approach.
Honors Thesis. East Carolina University,
December 2023. The Scholarship.
http://hdl.handle.net/10342/13302.
May 16, 2024.
Chicago:
Roberts, Davis Keith,
“Investigation of Neurodegenerative Disease-related Cofilin-Actin Rod Dynamics Using a Novel Optogenetic Approach”
(Honors Thesis., East Carolina University,
December 2023).
AMA:
Roberts, Davis Keith.
Investigation of Neurodegenerative Disease-related Cofilin-Actin Rod Dynamics Using a Novel Optogenetic Approach
[Honors Thesis]. Greenville, NC: East Carolina University;
December 2023.
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Publisher
East Carolina University