000007672 001__ 7672
000007672 005__ 20231129124935.0
000007672 0247_ $$2DOI$$a10.6083/m4vt1r61
000007672 037__ $$aETD
000007672 245__ $$aThe ALS-associated protein, TDP-43, functions to regulate drosophila larval motor behavior and physiology in a cacophony-dependent manner
000007672 260__ $$bOregon Health and Science University
000007672 269__ $$a2017
000007672 336__ $$aDissertation
000007672 502__ $$bPh.D.
000007672 520__ $$aAmyotrophic Lateral Sclerosis is the most common adult onset motor neurodegenerative disease. The etiology of the disease remains obscure, and as such there is no effective treatment or cure. TDP-43 is a nuclear RNA and DNA binding protein associated with 96% of ALS patient pathology. Tissue samples taken post-mortem from patients show a loss of nuclear localization and the presence of TDP-43 in cytoplasmic inclusions in the cell body. Whether the pathogenesis of the disease is driven by loss of nuclear function, gain of cytotoxicity with the formation of the cytoplasmic inclusions, or some other yet unidentified cause is not known. The goal of the research presented here was to understand the downstream effects of loss of nuclear TDP-43 function on motor behavior and physiology, using Drosophila melanogaster as a model. The results I present here show that behavioral motor defects associated with loss of Drosophila TDP-43 are driven by the loss of the voltage gated calcium channel cacophony, not at the neuromuscular junction, but rather in cells located centrally in the protocerebrum of the brain.
000007672 542__ $$fIn copyright - single owner
000007672 650__ $$aCalcium Channels$$028229
000007672 650__ $$aDrosophila$$018058
000007672 650__ $$aAmyotrophic Lateral Sclerosis$$014651
000007672 650__ $$aMotor Neurons$$022454
000007672 691__ $$aSchool of Medicine$$041369
000007672 692__ $$aDepartment of Physiology and Pharmacology$$041442
000007672 7001_ $$aLembke, Kayly M.
000007672 8564_ $$9fa59a4fc-6519-4939-a0cd-076459608455$$s8209395$$uhttps://digitalcollections.ohsu.edu/record/7672/files/Lembke.Kayly.2017.pdf
000007672 905__ $$a/rest/prod/6w/92/4c/30/6w924c30w
000007672 909CO $$ooai:digitalcollections.ohsu.edu:7672$$pstudent-work
000007672 980__ $$aTheses and Dissertations