Investigation of Neurodegenerative Disease-related Cofilin-Actin Rod Dynamics Using a Novel Optogenetic Approach

dc.access.optionOpen Access
dc.contributor.advisorHughes, Robert M
dc.contributor.authorRoberts, Davis Keith
dc.contributor.departmentChemistry
dc.date.accessioned2024-02-16T16:51:20Z
dc.date.created2023-12
dc.date.issued2023-12-15
dc.date.submittedDecember 2023
dc.date.updated2024-02-05T19:59:30Z
dc.degree.departmentChemistry
dc.degree.disciplineBiology
dc.degree.grantorEast Carolina University
dc.degree.levelUndergraduate
dc.degree.nameBS
dc.description.abstractThe 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.
dc.embargo.lift2024-12-01
dc.embargo.terms2024-12-01
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/10342/13302
dc.publisherEast Carolina University
dc.subjectneurodegenerative diseases
dc.subjectcofilin-actin abnormalities
dc.subjectcellular stress conditions
dc.titleInvestigation of Neurodegenerative Disease-related Cofilin-Actin Rod Dynamics Using a Novel Optogenetic Approach
dc.typeHonors Thesis
dc.type.materialtext

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