Induction and prevention of patterned neurodegeneration by amyloid precursor protein

Simple item page
dc.contributor.advisorPierce-Shimomura, Jonathan T.
dc.creatorCrisp, Ashley Aaronen
dc.date.accessioned2013-10-31T21:20:02Zen
dc.date.accessioned2017-05-11T22:35:40Z
dc.date.available2017-05-11T22:35:40Z
dc.date.issued2013-05en
dc.date.submittedMay 2013en
dc.date.updated2013-10-31T21:20:03Zen
dc.descriptiontexten
dc.description.abstractAlzheimer 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.departmentCellular and Molecular Biologyen
dc.format.mimetypeapplication/pdfen
dc.identifier.urihttp://hdl.handle.net/2152/21884en
dc.language.isoen_USen
dc.subjectC. elegansen
dc.subjectAlzheimer's Diseaseen
dc.subjectNeurodegenerationen
dc.subjectAmyloid precursor proteinen
dc.titleInduction and prevention of patterned neurodegeneration by amyloid precursor proteinen

Files

Collections

University of Texas at Austin