000003078 001__ 3078 000003078 005__ 20250424232814.0 000003078 0247_ $$2DOI$$a10.6083/g4pr-1p73 000003078 037__ $$aETD 000003078 245__ $$aIdentifying the pathogenic mechanisms of swiss-cheese phenotypes to understand neuropathy target esterase associated disorders 000003078 260__ $$bOregon Health and Science University 000003078 269__ $$a2018-05-01 000003078 336__ $$aDissertation 000003078 502__ $$bPh.D. 000003078 520__ $$aNeuropathy Target Esterase (NTE) is an enzyme localized to the ER that regulates Protein Kinase A (PKA) signaling and maintains lipid homeostasis. Exposure to a neurotoxic organophosphate or mutations in NTE cause a spectrum of disorders with neurodegenerative symptoms ranging from blindness, hypogonadism, and cerebellar atrophy to motor neuron loss. Understanding how the functions of NTE are affected by a chemical or mutations and the mechanisms of pathology is important for the identification of pathways and development of therapeutic strategies. Loss of NTE’s ortholog, Swiss-Cheese (SWS), in Drosophila melanogaster causes a dysregulation of PKA signaling, an increase in phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) levels and eventual age-dependent neurodegeneration. The goal of this research was to use Drosophila to understand the etiology of NTE disorders. 000003078 542__ $$fIn copyright - single owner 000003078 650__ $$aDrosophila$$018058 000003078 650__ $$aDrosophila melanogaster$$018059 000003078 650__ $$aHypogonadism$$020570 000003078 650__ $$aNeurodegenerative Diseases$$031750 000003078 650__ $$aOrganophosphates$$024056 000003078 650__ $$aHomeostasis$$020285 000003078 650__ $$aCyclic AMP-Dependent Protein Kinases$$030307 000003078 650__ $$aneurotoxic esterase 000003078 691__ $$aSchool of Medicine$$041369 000003078 692__ $$aDepartment of Molecular and Medical Genetics$$041428 000003078 7001_ $$aSunderhaus, Elizabeth$$uOregon Health and Science University$$041354 000003078 7201_ $$aKretzschmar, Doris$$uOregon Health and Science University$$041354$$7Personal$$eAdvisor 000003078 7201_ $$aMorton, David B.$$uOregon Health and Science University$$041354$$7Personal$$eCommittee chair 000003078 7201_ $$aHayflick, Susan$$uOregon Health and Science University$$041354$$7Personal$$eCommittee member 000003078 7201_ $$aLogan, Mary$$uOregon Health and Science University$$041354$$7Personal$$eCommittee member 000003078 7201_ $$aMcCullough, Amanda$$uOregon Health and Science University$$041354$$7Personal$$eCommittee member 000003078 8564_ $$9c99a0104-50a0-4ee5-b03f-8660132d871b$$s4202619$$uhttps://digitalcollections.ohsu.edu/record/3078/files/4011_etd.pdf$$ePublic$$2cd6b898e0f0cda15a75b56432abf37f3$$31 000003078 905__ $$a/rest/prod/2f/75/r8/29/2f75r829s 000003078 909CO $$ooai:digitalcollections.ohsu.edu:3078$$pstudent-work 000003078 980__ $$aTheses and Dissertations