Genomes and Genes
Christopher B Eckman
Affiliation: Mayo Clinic
- Degradation of the Alzheimer's amyloid beta peptide by endothelin-converting enzymeE A Eckman
Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
J Biol Chem 276:24540-8. 2001..Finally, we show that recombinant soluble ECE-1 is capable of hydrolyzing synthetic Abeta40 and Abeta42 in vitro at multiple sites...
- An update on the amyloid hypothesisChristopher B Eckman
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
Neurol Clin 25:669-82, vi. 2007....
- Alzheimer's disease beta-amyloid peptide is increased in mice deficient in endothelin-converting enzymeElizabeth A Eckman
Mayo Clinic Jacksonville, Florida 32224, USA
J Biol Chem 278:2081-4. 2003....
- Abeta-degrading enzymes: modulators of Alzheimer's disease pathogenesis and targets for therapeutic interventionE A Eckman
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA
Biochem Soc Trans 33:1101-5. 2005..In this paper, we will review the roles of NEP, IDE, ECE and plasmin in determining endogenous Abeta concentration, highlighting recent results concerning the regulation of these enzymes and their potential as therapeutic targets...
- Regulation of steady-state beta-amyloid levels in the brain by neprilysin and endothelin-converting enzyme but not angiotensin-converting enzymeElizabeth A Eckman
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
J Biol Chem 281:30471-8. 2006....
- Single-dose intracerebroventricular administration of galactocerebrosidase improves survival in a mouse model of globoid cell leukodystrophyWing C Lee
Mayo Clinic College of Medicine, 4500 San Pablo Rd, Jacksonville, Florida 32224, USA
FASEB J 21:2520-7. 2007..These results indicate that even a single i.c.v. administration of the recombinant enzyme can have significant clinical impact and suggests that other lysosomal storage disorders with significant CNS involvement may similarly benefit...
- Hepatic arterial reconstruction for orthotopic liver transplantation in the ratTomohide Hori
Department of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida 32224, USA
J Surg Res 178:907-14. 2012..Orthotopic liver transplantation (OLT) models in rats have been investigated in many studies. The reconstruction of hepatic artery is required for reliable OLT and also requires advanced skills...
- Suppression of galactosylceramidase (GALC) expression in the twitcher mouse model of globoid cell leukodystrophy (GLD) is caused by nonsense-mediated mRNA decay (NMD)Wing C Lee
Department of Pharmacology, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
Neurobiol Dis 23:273-80. 2006....
- Reductions in levels of the Alzheimer's amyloid beta peptide after oral administration of ginsenosidesFeng Chen
Mayo Clinic College of Medicine, Department of Pharmacology, Birdsall Bldg Rm 327, 4500 San Pablo Rd, Jacksonville, Florida 32224, USA
FASEB J 20:1269-71. 2006..The results indicate that ginseng itself, or purified ginsenosides, may have similarly useful effects in human disease...
- The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteinsChad A Dickey
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
J Clin Invest 117:648-58. 2007....
- Molecular characterization of mutations that cause globoid cell leukodystrophy and pharmacological rescue using small molecule chemical chaperonesWing C Lee
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA
J Neurosci 30:5489-97. 2010..This study suggests that mutations in GALC can cause GLD by impairing protein processing and/or folding and that pharmacological chaperones may be potential therapeutic agents for patients carrying certain mutations...
- Abeta42 is essential for parenchymal and vascular amyloid deposition in miceEileen McGowan
Department Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
Neuron 47:191-9. 2005..These data establish that Abeta1-42 is essential for amyloid deposition in the parenchyma and also in vessels...
- Natural product extracts that reduce accumulation of the Alzheimer's amyloid beta peptide: selective reduction in A beta42Debra Yager
Mayo Clinic Jacksonville, FL 32224, USA
J Mol Neurosci 19:129-33. 2002..In addition, we have identified one extract that selectively reduces A beta42. Intracerebroventricular administration of this agent to mice results in a selective reduction in A beta42 in the brain...
- Altered expression of zonula occludens-2 precedes increased blood-brain barrier permeability in a murine model of fulminant hepatic failureNaoki Shimojima
Department of Transplantation, Division of Transplant Surgery, Mayo Clinic College of Medicine, Jacksonville, FL 32216, USA
J Invest Surg 21:101-8. 2008..Significant alterations in ZO-2 expression and distribution in the tight junctions preceded the increased BBB permeability in FHF mice. These results suggest that ZO-2 may play an important role in the pathogenesis of brain edema in FHF...
- Occludin is regulated by epidermal growth factor receptor activation in brain endothelial cells and brains of mice with acute liver failureFeng Chen
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
Hepatology 53:1294-305. 2011..Similar EGFR activation and p38 MAPK/NFκB activation were found in the brains of ALF mice, and these changes were attenuated with GM6001 treatment...
- Matrix metalloproteinase-9 contributes to brain extravasation and edema in fulminant hepatic failure miceJustin H Nguyen
Department of Transplantation, Division of Transplant Surgery, Mayo Clinic College of Medicine, 4205 Belfort Road, Suite 1100, Jacksonville, FL 32216, USA
J Hepatol 44:1105-14. 2006..Mechanisms of brain extravasation leading to brain edema remain incompletely understood. Matrix metalloproteinase (MMP)-9 is implicated in various brain injuries. We hypothesized that MMP-9 contributes to brain edema in FHF...
- Comprehensive and innovative techniques for liver transplantation in rats: a surgical guideTomohide Hori
Department of Neuroscience, Mayo Clinic, Birdsall Research Building, Room 323, 4500 San Pablo Road, Jacksonville, Florida, FL 32224, United States
World J Gastroenterol 16:3120-32. 2010..To investigate our learning curves of orthotopic liver transplantation (OLT) in rats and the most important factor for successful surgery...
- Physiologic and pathologic events mediated by intramembranous and juxtamembranous proteolysisTodd E Golde
Mayo Clinic Jacksonville, Department of Neuroscience, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Sci STKE 2003:RE4. 2003..Because some of the proteases mediating IP and JP can be selectivity inhibited, inhibitors targeting these proteases are likely to alter both physiologic and pathologic events triggered by IP and JP...
- Agonist-induced restoration of hippocampal neurogenesis and cognitive improvement in a model of cholinergic denervationJackalina M Van Kampen
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32246, USA
Neuropharmacology 58:921-9. 2010....
- Dopamine D3 receptor agonist delivery to a model of Parkinson's disease restores the nigrostriatal pathway and improves locomotor behaviorJackalina M Van Kampen
Department of Pharmacology, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
J Neurosci 26:7272-80. 2006....
- Development of a high throughput drug screening assay for the detection of changes in tau levels -- proof of concept with HSP90 inhibitorsChad A Dickey
Mayo Clinic College of Medicine, FL 32224, USA
Curr Alzheimer Res 2:231-8. 2005..Using this assay, we have demonstrated that a class of HSP90 inhibitors is able to significantly lower intracellular tau levels most likely through induction of a heat shock response...
- Enzyme replacement therapy results in substantial improvements in early clinical phenotype in a mouse model of globoid cell leukodystrophyWing C Lee
Mayo Clinic College of Medicine, Department of Pharmacology, Jacksonville, Florida, USA
FASEB J 19:1549-51. 2005..These results indicate that peripheral ERT is likely to be beneficial in GLD...
- Amyloid-beta peptide levels in brain are inversely correlated with insulysin activity levels in vivoBonnie C Miller
Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas 75390 9151, USA
Proc Natl Acad Sci U S A 100:6221-6. 2003..These findings indicate that there is an inverse correlation between in vivo insulysin activity levels and brain Abeta peptide levels and suggest that modulation of insulysin activity may alter the risk for Alzheimer's disease...
- Partial loss-of-function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-proteinWesley Farris
Department of Neurology, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
Am J Pathol 164:1425-34. 2004..Our findings have relevance for the emerging genetic evidence suggesting that IDE may be a late-onset AD-risk gene, and for the epidemiological relationships among hyperinsulinemia, DM2, and AD...
- Differential expression of cholesterol hydroxylases in Alzheimer's diseaseJames Brown
Departments of Pharmacology and Pathology, Loyola University Medical Center, Maywood, IL 60153, USA
J Biol Chem 279:34674-81. 2004....
- The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer's diseaseBirgit Hutter-Paier
JSW Research Forschungslabor GmbH, Institute of Experimental Pharmacology, Rankengasse 28, 8020 Graz, Austria
Neuron 44:227-38. 2004..Our results suggest that ACAT inhibition may be effective in the prevention and treatment of AD by inhibiting generation of the Abeta peptide...
- The secreted beta-amyloid precursor protein ectodomain APPs alpha is sufficient to rescue the anatomical, behavioral, and electrophysiological abnormalities of APP-deficient miceSabine Ring
Department of Bioinformatics and Functional Genomics, Institute for Pharmacy and Molecular Biotechnology, University of Heidelberg, D 69120 Heidelberg, Germany
J Neurosci 27:7817-26. 2007..Together, our data suggest that the APP C terminus is dispensable and that APPs alpha is sufficient to mediate the physiological functions of APP assessed by these tests...
- Endothelin-converting enzyme 1 degrades neuropeptides in endosomes to control receptor recyclingDirk Roosterman
Department of Dermatology, Interdisziplinäres Zentrum für Klinische Forschung Münster, and Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University of Munster, Von Esmarch Strasse 58, 48149 Munster, Germany
Proc Natl Acad Sci U S A 104:11838-43. 2007..Antagonism of these endosomal processes represents a strategy for inhibiting sustained signaling of receptors, and defects may explain the tachyphylaxis of drugs that are receptor agonists...
- Cellular prion protein regulates beta-secretase cleavage of the Alzheimer's amyloid precursor proteinEdward T Parkin
Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, United Kingdom
Proc Natl Acad Sci U S A 104:11062-7. 2007..In conclusion, this is a mechanism by which the cellular production of the neurotoxic Abeta is regulated by PrP(C) and may have implications for both Alzheimer's and prion diseases...
- Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivoWesley Farris
Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 100:4162-7. 2003....
- Generation of the beta-amyloid peptide and the amyloid precursor protein C-terminal fragment gamma are potentiated by FE65L1Yang Chang
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129 4404, USA
J Biol Chem 278:51100-7. 2003..Finally, although FE65L1 increases APP C-terminal domain production, it does not mediate the APP-dependent transcriptional activation observed with FE65...
- Testosterone, but not nonaromatizable dihydrotestosterone, improves working memory and alters nerve growth factor levels in aged male ratsHeather A Bimonte-Nelson
Department of Physiology and Neuroscience and the Center for Studies on Aging, Medical University of South Carolina, Charleston 29425, USA
Exp Neurol 181:301-12. 2003....
- Estrogen regulates neprilysin activity in rat brainJian Huang
College of Life Science, Wuhan University, Wuhan, PR China
Neurosci Lett 367:85-7. 2004..Estrogen replacement restores neprilysin levels back to control values. These changes in neprilysin activity suggest that in women estrogen is required to maintain basal levels of neprilysin...
- Behavioral and neurobiological markers of Alzheimer's disease in Ts65Dn mice: effects of estrogenChristopher L Hunter
Department of Physiology and Neuroscience and the Center on Aging, Medical University of South Carolina, 26 Bee Street, Charleston, SC 29425, USA
Neurobiol Aging 25:873-84. 2004..These findings further support Ts65Dn mice as a model for specific AD-like symptoms, and demonstrate that estrogen treatment of this type does not improve the cognitive ability of male Ts65Dn mice...
- Cerebrospinal fluid drainage and cranial decompression prolong survival in rats with fulminant hepatic failureSatoshi Yamamoto
Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Transpl Int 19:675-82. 2006..5 h (P = 0.031), and 69.4 +/- 3.9 vs. 53.7 +/- 3.2 h (P = 0.009), respectively. In conclusion, these findings suggest that CSF drainage and decompressive craniectomy may increase the window of opportunity for liver transplantation...
- Essential roles for the FE65 amyloid precursor protein-interacting proteins in brain developmentSuzanne Guenette
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA 02129 4404, USA
EMBO J 25:420-31. 2006..The defects observed in the double knockout may also involve the family of Ena/Vasp proteins, which participate in actin cytoskeleton remodeling and interact with the WW domains of FE65 proteins...
- Protein Tranduction for Treatment of Krabbe DiseaseChristopher Eckman; Fiscal Year: 2004..The lessons learned from these experiments may be useful for other diseases where delivery of a therapeutic protein may be desired, such as Alzheimer's disease and Parkinson's. ..
- Protein Misprocessing in Krabbe DiseaseChristopher Eckman; Fiscal Year: 2007..Further we propose to determine the subcellular localization of this increased activity to determine if the enzyme has reached its proper location and to monitor natural substrate cleavage as a prelude to in vivo testing. ..