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dc.creatorMarino, Claudia
dc.date.accessioned2019-08-19T18:27:00Z
dc.date.created2019-05
dc.date.submittedMay 2019
dc.identifier.urihttps://hdl.handle.net/2152.3/11215
dc.description.abstractAlzheimer’s disease (AD) is a devastating neurodegenerative disorder leading to dementia, affecting millions of individuals worldwide. Currently, there are no successful disease-modifying therapies, due to the complexity of biochemical alterations and risk factors leading to AD. One of the earliest alterations leading to AD is the synaptotoxic effect of amyloid beta oligomers (Abo). These oligomers are formed by the misfolding and subsequent aggregation of Ab, a cleavage product of the amyloid precursor protein (APP). Furthermore, compelling evidence suggests that an age-related failure of the protein quality control machinery could also contribute to the onset of AD, thus supporting the hypothesis that the main risk factor of late-onset AD is aging. Chaperones are critical components of the protein quality control machinery known to target misfolding proteins and to preserve cellular homeostasis. Here, we focused on the mitochondrial chaperone Hsp60, which is known to protect mitochondria from misfolded proteins. Evidence suggests that Hsp60 directly interacts with APP/Ab in vitro, and this interaction could contribute to protecting mitochondria from Ab-induced damage. However, weather Hsp60 interacts with Abo thus preventing the downstream synaptic toxicity is still unknown. In the current work, we aimed to characterize the effect of Hsp60 on Ab aggregation and if Hsp60- Abo interaction could reduce the downstream toxic effect of Abo at the synapses. Using spectroscopy, atomic force microscopy and chromatographic techniques we characterized the effect of Hsp60 on the aggregation pathway of Ab. We further tested the effect of Hsp60 on naturally secreted Abo in vitro using immunocytochemistry, western blotting, and ELISA. As Abo are known to bind to the synapses, impair synaptic plasticity and cause synaptic toxicity, we also tested if the interaction between these two proteins contributed to a change of Abo conformation, thus resulting in a change of downstream toxicity. Overall, our findings support that Hsp60 effectively targets Ab, thus resulting in protection of Abo-derived toxicity and propose Hsp60 as an attractive candidate for future therapies aiming in targeting Abo toxicity.
dc.format.mimetypeapplication/pdf
dc.subjectAlzheimer's disease
dc.subjectchaperone
dc.subjectamyloid
dc.subjectoligomer: Hsp60
dc.titleThe role of Hsp60 in Amyloid beta toxicity: Relevance to Alzheimer’s disease
dc.typeThesis
dc.date.updated2019-08-19T18:27:01Z
dc.type.materialtext
thesis.degree.nameNeuroscience (Doctoral)
thesis.degree.levelDoctoral
thesis.degree.grantorThe University of Texas Medical Branch at Galveston
thesis.degree.departmentNeuroscience
dc.creator.orcid0000-0002-2332-2163
local.embargo.terms2022-05-01
local.embargo.lift2022-05-01


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