Induction and prevention of patterned neurodegeneration by amyloid precursor protein
| dc.contributor.advisor | Pierce-Shimomura, Jonathan T. | |
| dc.creator | Crisp, Ashley Aaron | en |
| dc.date.accessioned | 2013-10-31T21:20:02Z | en |
| dc.date.issued | 2013-05 | en |
| dc.date.submitted | May 2013 | en |
| dc.date.updated | 2013-10-31T21:20:03Z | en |
| dc.description | text | en |
| dc.description.abstract | Alzheimer disease is characterized by the initial degeneration of a subset of cholinergic neurons. This pattern of degeneration can be triggered by overexpression of the amyloid precursor protein (APP) gene in humans. Interestingly, APP is widely expressed; it is therefore unclear why only certain cholinergic neurons are vulnerable to degeneration. We show that widespread expression of the human APP gene in the nematode Caenorhabditis elegans also induces age-dependent apoptotic degeneration of select cholinergic neurons. Identical results were obtained by overexpressing the orthologous worm gene apl-1. The pattern of neurodegeneration matched the cell-autonomous accumulation of APP protein in vulnerable neurons and could be activated cell-non-autonomously by distinct portions of APP. Vulnerability to APP accumulation and degeneration depended inversely on the level of ASK1/p38MAPK innate-immune signaling in cholinergic neurons. Lastly, we identify a compound P7C3 that blocks entrance to apoptosis caused by APP or immunodeficiency. Our results suggest that immunosenescence sculpts the cellular pattern of neurodegeneration by APP. | en |
| dc.description.department | Cellular and Molecular Biology | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.uri | http://hdl.handle.net/2152/21884 | en |
| dc.language.iso | en_US | en |
| dc.subject | C. elegans | en |
| dc.subject | Alzheimer's Disease | en |
| dc.subject | Neurodegeneration | en |
| dc.subject | Amyloid precursor protein | en |
| dc.title | Induction and prevention of patterned neurodegeneration by amyloid precursor protein | en |
| thesis.degree.department | Cellular and Molecular Biology | en |
| thesis.degree.discipline | Cell and Molecular Biology | en |
| thesis.degree.grantor | The University of Texas at Austin | en |
| thesis.degree.level | Doctoral | en |
| thesis.degree.name | Doctor of Philosophy | en |