Photo of Doris E. Kretzschmar, Ph.D.

Doris E. Kretzschmar Ph.D.

  • (503) 494-0243
    • Associate Professor Oregon Institute of Occupational Health Sciences
    • Associate Professor of Molecular and Medical Genetics School of Medicine
    • Molecular and Medical Genetics Graduate Program School of Medicine
    • Neuroscience Graduate Program School of Medicine
    • Program in Molecular and Cellular Biosciences School of Medicine

We are using Drosophila to study basic mechanisms of neurodegeneration. Currently, we are focusing on two projects. One is the characterization of the swiss cheese mutant, which shows progressive degeneration of the adult nervous system. SWS is the fly homolog of a ´human gene called Neuropathy Target Esterase which plays a role in neurodegeneration induced by pesticides and nerve agents.  Recent results indicated that SWS/NTE interfere with membrane composition thereby damaging neurons.  We are now studying in detail how this leads to neuronal degeneration and cell death.  The other project focuses on the function of Amyloid Precursor Proteins, which are key factors in Alzheimer's Disease.  We are investigating how these proteins are processed , what function different fragments derived from this large precursor protein have, and what other genes influence these processes.  In addition, we have developed a system to study the transport of this protein and its fragments in the living brain using confocal imaging.

Education

  • Ph.D., Univeristy of Wüerzburg, Wüerzburg Germany 1999

Publications

  • "Animal Models of Alzheimer's Disease."   Animal Models for the Study of Human Disease: Second Edition. Elsevier Inc., 2017. p. 1031-1085.
  • "NTE/PNPLA6 is expressed in mature Schwann cells and is required for glial ensheathment of Remak fibers." GLIA  In: , 2017.
  • "Reduced expression of foxpl as a contributing factor in huntington’s disease." Journal of Neuroscience In: , Vol. 37, No. 27, 2017, p. 6575-6587.
  • "Mass histology to quantify neurodegeneration in drosophila." Journal of Visualized Experiments  In: , Vol. 2016, No. 118, e54809, 15.12.2016.
  • "Amyloid precursor proteins are dynamically trafficked and processed during neuronal development." Frontiers in Molecular Neuroscience In: , Vol. 9, No. NOV2016, 130, 25.11.2016.
  • "Analysis of amyloid precursor protein function in Drosophila melanogaster." Frontiers in Molecular Neuroscience  In: , Vol. 9, No. JUL, 61, 26.07.2016.
  • "Glial expression of Swiss cheese (SWS), the Drosophila orthologue of neuropathy target esterase (NTE), is required for neuronal ensheathment and function." DMM Disease Models and Mechanisms  In: , Vol. 9, No. 3, 01.03.2016, p. 283-294.
  • "The genetic basis of cerebral palsy." Developmental Medicine and Child Neurology In: , 2016.
  • "Manipulations of amyloid precursor protein cleavage disrupt the circadian clock in aging Drosophila." Neurobiology of Disease In: , Vol. 77, 01.05.2015, p. 117-126.
  • "Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness." Nature Communications  In: , Vol. 6, 5614, 08.01.2015.
  • "Loss of tau results in defects in photoreceptor development and progressive neuronal degeneration in Drosophila." Developmental Neurobiology  In: , Vol. 74, No. 12, 01.12.2014, p. 1210-1225.
  • "Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome." Journal of Clinical Endocrinology and Metabolism In: , Vol. 99, No. 10, 01.10.2014, p. E2067-E2075.
  • "Relationships between the circadian system and Alzheimer's disease-like symptoms in Drosophila." PLoS One In: , Vol. 9, No. 8, e106068, 29.08.2014.
  • "Increased actin polymerization and stabilization interferes with neuronal function and survival in the AMPKγ mutant loechrig." PLoS One  In: , Vol. 9, No. 2, e89847, 25.02.2014.
  • "Organophosphate-induced changes in the PKA regulatory function of Swiss Cheese/NTE lead to behavioral deficits and neurodegeneration." PLoS One  In: , Vol. 9, No. 2, e87526, 18.02.2014.
  • "Mutations in gamma adducin are associated with inherited cerebral palsy." Annals of Neurology  In: , Vol. 74, No. 6, 12.2013, p. 805-814.
  • "Models of Alzheimer's Disease."   Animal Models for the Study of Human Disease. Elsevier Inc., 2013. p. 595-632.
  • "β-secretase cleavage of the fly amyloid precursor protein is required for glial survival." Journal of Neuroscience  In: , Vol. 32, No. 46, 14.11.2012, p. 16181-16192.
  • "Increased RhoA Prenylation in the loechrig (loe) Mutant Leads to Progressive Neurodegeneration." PLoS One  In: , Vol. 7, No. 9, e44440, 06.09.2012.
  • "Proximal giant neurofilamentous axonopathy in mice genetically engineered to resist calpain and caspase cleavage of α-II spectrin." Journal of Molecular Neuroscience In: , Vol. 47, No. 3, 07.2012, p. 631-638.
  • "Analysis of amyloid precursor protein function in Drosophila melanogaster." Experimental Brain Research  In: , Vol. 217, No. 3-4, 04.2012, p. 413-421.
  • "Amyloid precursor proteins are protective in Drosophila models of progressive neurodegeneration." Neurobiology of Disease  In: , Vol. 46, No. 1, 04.2012, p. 78-87.
  • "Loss of circadian clock accelerates aging in neurodegeneration-prone mutants." Neurobiology of Disease In: , Vol. 45, No. 3, 03.2012, p. 1129-1135.
  • "Drosophila GGA Model : An Ultimate Gateway to GGA Analysis." Traffic In: , Vol. 12, No. 12, 12.2011, p. 1821-1838.
  • "A translational continuum of model systems for evaluating treatment strategies in Alzheimer's disease : Isradipine as a candidate drug." DMM Disease Models and Mechanisms In: , Vol. 4, No. 5, 09.2011, p. 634-648.
  • "Alzheimer's Disease and tauopathy studies in flies and worms." Neurobiology of Disease  In: , Vol. 40, No. 1, 10.2010, p. 21-28.
  • "Identification of novel 1,4-benzoxazine compounds that are protective in tissue culture and in vivo models of neurodegeneration." Journal of Neuroscience Research In: , Vol. 88, No. 9, 07.2010, p. 1970-1984.
  • "The circadian clock gene period extends healthspan in aging Drosophila melanogaster." Aging In: , Vol. 1, No. 11, 11.2009, p. 937-948.
  • "Swiss cheese et allii, some of the first neurodegenerative mutants isolated in Drosophila." Journal of Neurogenetics  In: , Vol. 23, No. 1-2, 03.2009, p. 34-41.
  • "Neurotoxic effects induced by the Drosophila amyloid-β peptide suggest a conserved toxic function." Neurobiology of Disease  In: , Vol. 33, No. 2, 02.2009, p. 274-281.

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