Date of Award
Spring 5-2015
Degree Type
Honors College Thesis
Department
Chemistry and Biochemistry
First Advisor
Vijay Rangachari
Advisor Department
Chemistry and Biochemistry
Abstract
Alzheimer disease (AD) is a neurodegenerative disorder characterized by severe memory deficit and cognitive decline among the elderly. This degeneration is caused by the aggregation and deposition of a protein called amyloid-β (Aβ) in the brain. Aggregation of Aβ causes neuroinflammation in addition to other toxic events. However, it is unclear whether inflammation from an external source, such as from a traumatic brain injury (TBI), could trigger Aβ aggregation. In this context, several pro-inflammatory mediators such as cytokines and chemokines have been suspects. It is now hypothesized that a group of proteins called granulins (Grns) are unique inflammatory mediators that can interact and modulate Aβ aggregation. Grns are a family of seven (A-G) small, cysteine-rich proteins that are proteolytically cleaved from a precursor protein called progranulin (PGrn) during neuroinflammation. Grns have been implicated in both AD and frontotemporal lobar degeneration (FTLD). Among the seven Grns, my work is primarily focused on GrnE. GrnE was recombinantly expressed in E. coli and purified using affinity chromatography. The structural characteristics were studied using several biochemical and biophysical techniques, such as sodium dodecyl sulfate (SDS) and native gel electrophoresis, circular dichroism (CD), and fluorescence spectroscopy. The collective data suggest that GrnE is an intrinsically disordered protein (IDP) and is able to dimerize at high concentrations. This is a novel finding because GrnE is not expected to be disordered due to its high degree of intramolecular disulfide bonds. Additionally, Grns C and F have been successfully expressed in E. coli.
Copyright
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Recommended Citation
Reed, Randi G., "Granulins as Inflammatory Mediators in Alzheimer Disease" (2015). Honors Theses. 293.
https://aquila.usm.edu/honors_theses/293