<p>Parkinson’s disease is a neurodegenerative disorder
characterized by a loss of dopaminergic neurons, where mitochondrial
dysfunction and neuroinflammation are implicated in this process. However, the
exact mechanisms of mitochondrial dysfunction, oxidative stress and
neuroinflammation leading to the onset and development of Parkinson’s disease
are not well understood. There is a lack of tools necessary to dissect these
mechanisms, therefore we engineered genetically encoded fluorescent biosensors
to monitor redox status and an inflammatory signal peptide with high
spatiotemporal resolution. To measure intracellular redox dynamics, we
developed red-shifted redox sensors and demonstrated their application in dual
compartment imaging to study cross compartmental redox dynamics in live cells.
To monitor extracellular inflammatory events, we developed a family of
spectrally diverse genetically encoded fluorescent biosensors for the
inflammatory mediator peptide, bradykinin. At the organismal level, we characterized the locomotor effects of mitochondrial toxicant-induced
dopaminergic disruption in a zebrafish animal model and evaluated a behavioral
assay as a method to screen for dopaminergic dysfunction. Pairing our
intracellular redox sensors and our extracellular bradykinin sensors in a
Parkinson’s disease animal model, such as a zebrafish toxicant-induced model will
prove useful for dissecting the role of mitochondrial dysfunction and
inflammation in Parkinson’s disease. </p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/7763471 |
| Date | 10 June 2019 |
| Creators | Stevie Norcross (6395171) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/ENGINEERING_GENETICALLY_ENCODED_FLUORESCENT_BIOSENSORS_TO_STUDY_THE_ROLE_OF_MITOCHONDRIAL_DYSFUNCTION_AND_INFLAMMATION_IN_PARKINSON_S_DISEASE/7763471 |
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