Jochen Walter

Summary

Affiliation: University of Bonn
Country: Germany

Publications

  1. ncbi request reprint Control of amyloid-beta-peptide generation by subcellular trafficking of the beta-amyloid precursor protein and beta-secretase
    Jochen Walter
    Department of Neurology, University of Bonn, Bonn, Germany
    Neurodegener Dis 3:247-54. 2006
  2. pmc Interactions between APP secretases and inflammatory mediators
    Magdalena Sastre
    Division of Neuroscience and Mental Health, Imperial College London, The Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    J Neuroinflammation 5:25. 2008
  3. pmc Phosphorylation of amyloid beta (Aβ) peptides - a trigger for formation of toxic aggregates in Alzheimer's disease
    Sathish Kumar
    Department of Neurology, University of Bonn, Germany
    Aging (Albany NY) 3:803-12. 2011
  4. pmc Casein kinase 2 dependent phosphorylation of neprilysin regulates receptor tyrosine kinase signaling to Akt
    Martin Siepmann
    Department of Neurology, Molecular Cell Biology, University of Bonn, Bonn, Germany
    PLoS ONE 5:. 2010
  5. pmc Cross-talk of membrane lipids and Alzheimer-related proteins
    Jochen Walter
    Department of Neurology, University of Bonn, Sigmund Freud Str, 25, 53127, Bonn, Germany
    Mol Neurodegener 8:34. 2013
  6. ncbi request reprint γ-Secretase, apolipoprotein E and cellular cholesterol metabolism
    Jochen Walter
    Department of Neurology, University of Bonn, Germany
    Curr Alzheimer Res 9:189-99. 2012
  7. ncbi request reprint GGA1 is expressed in the human brain and affects the generation of amyloid beta-peptide
    Tina Wahle
    Department of Neurology, University of Bonn, 53127 Bonn, Germany
    J Neurosci 26:12838-46. 2006
  8. ncbi request reprint Loss of gamma-secretase function impairs endocytosis of lipoprotein particles and membrane cholesterol homeostasis
    Irfan Y Tamboli
    Department of Neurology, University of Bonn, 53127 Bonn, Germany
    J Neurosci 28:12097-106. 2008
  9. pmc Statins promote the degradation of extracellular amyloid {beta}-peptide by microglia via stimulation of exosome-associated insulin-degrading enzyme (IDE) secretion
    Irfan Y Tamboli
    Departments of Neurology, University of Bonn, Sigmund Freud Strasse 25, 53127 Bonn, Germany
    J Biol Chem 285:37405-14. 2010
  10. pmc Phosphorylation of amyloid-β peptide at serine 8 attenuates its clearance via insulin-degrading and angiotensin-converting enzymes
    Sathish Kumar
    Department of Neurology, University of Bonn, 53127 Bonn, Germany
    J Biol Chem 287:8641-51. 2012

Collaborators

Detail Information

Publications37

  1. ncbi request reprint Control of amyloid-beta-peptide generation by subcellular trafficking of the beta-amyloid precursor protein and beta-secretase
    Jochen Walter
    Department of Neurology, University of Bonn, Bonn, Germany
    Neurodegener Dis 3:247-54. 2006
    ..Here, I summarize and discuss these findings in the context of other studies focused on the function of BACE1 and BACE2 and the role of subcellular trafficking in the proteolytic processing of betaAPP...
  2. pmc Interactions between APP secretases and inflammatory mediators
    Magdalena Sastre
    Division of Neuroscience and Mental Health, Imperial College London, The Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    J Neuroinflammation 5:25. 2008
    ..In this review we will discuss some of these issues and the role of the secretases in inflammation, independent of their effect on Abeta formation...
  3. pmc Phosphorylation of amyloid beta (Aβ) peptides - a trigger for formation of toxic aggregates in Alzheimer's disease
    Sathish Kumar
    Department of Neurology, University of Bonn, Germany
    Aging (Albany NY) 3:803-12. 2011
    ..The identification of extracellular protein kinase A should also stimulate pharmacological approaches to decrease Aβ phosphorylation in the therapy and/or prevention of AD...
  4. pmc Casein kinase 2 dependent phosphorylation of neprilysin regulates receptor tyrosine kinase signaling to Akt
    Martin Siepmann
    Department of Neurology, Molecular Cell Biology, University of Bonn, Bonn, Germany
    PLoS ONE 5:. 2010
    ..Thus, our data demonstrate a regulatory role of CK2 in the interaction of NEP with PTEN and insulin/IGF-1 signaling...
  5. pmc Cross-talk of membrane lipids and Alzheimer-related proteins
    Jochen Walter
    Department of Neurology, University of Bonn, Sigmund Freud Str, 25, 53127, Bonn, Germany
    Mol Neurodegener 8:34. 2013
    ..Here, we review the close connection of cellular lipid metabolism and AD associated proteins and discuss potential mechanisms that could contribute to initiation and progression of AD. ..
  6. ncbi request reprint γ-Secretase, apolipoprotein E and cellular cholesterol metabolism
    Jochen Walter
    Department of Neurology, University of Bonn, Germany
    Curr Alzheimer Res 9:189-99. 2012
    ..It is hypothesized that γ-secretase activity is critically involved in cellular lipid homeostasis and that impaired lipid metabolism contributes to the pathogenesis of AD...
  7. ncbi request reprint GGA1 is expressed in the human brain and affects the generation of amyloid beta-peptide
    Tina Wahle
    Department of Neurology, University of Bonn, 53127 Bonn, Germany
    J Neurosci 26:12838-46. 2006
    ..Thus, GGA proteins might be involved in the pathogenesis of AD...
  8. ncbi request reprint Loss of gamma-secretase function impairs endocytosis of lipoprotein particles and membrane cholesterol homeostasis
    Irfan Y Tamboli
    Department of Neurology, University of Bonn, 53127 Bonn, Germany
    J Neurosci 28:12097-106. 2008
    ..Thus, these data demonstrate a functional link between two major genetic factors that cause early-onset and late-onset Alzheimer's disease...
  9. pmc Statins promote the degradation of extracellular amyloid {beta}-peptide by microglia via stimulation of exosome-associated insulin-degrading enzyme (IDE) secretion
    Irfan Y Tamboli
    Departments of Neurology, University of Bonn, Sigmund Freud Strasse 25, 53127 Bonn, Germany
    J Biol Chem 285:37405-14. 2010
    ..These data demonstrate a novel pathway for the nonconventional secretion of IDE via exosomes. The modulation of this pathway could provide a new strategy to enhance the extracellular clearance of Aβ...
  10. pmc Phosphorylation of amyloid-β peptide at serine 8 attenuates its clearance via insulin-degrading and angiotensin-converting enzymes
    Sathish Kumar
    Department of Neurology, University of Bonn, 53127 Bonn, Germany
    J Biol Chem 287:8641-51. 2012
    ..The inhibition of extracellular Aβ phosphorylation, stimulation of protease expression and/or their proteolytic activity could be explored to promote Aβ degradation in AD therapy or prevention...
  11. ncbi request reprint Sphingolipid storage impairs autophagic clearance of Alzheimer-associated proteins
    Irfan Y Tamboli
    Department of Neurology, University of Bonn, Germany
    Autophagy 7:645-6. 2011
    ..Thus, SL storage could promote the accumulation of Ab in endosomal and lysosomal compartments and thereby induce characteristic cytopathological changes of AD...
  12. pmc Extracellular phosphorylation of the amyloid β-peptide promotes formation of toxic aggregates during the pathogenesis of Alzheimer's disease
    Sathish Kumar
    Department of Neurology, University of Bonn, Bonn, Germany
    EMBO J 30:2255-65. 2011
    ..Phosphorylation of Aβ could represent an important molecular mechanism in the pathogenesis of the most common sporadic form of AD...
  13. ncbi request reprint A structural switch of presenilin 1 by glycogen synthase kinase 3beta-mediated phosphorylation regulates the interaction with beta-catenin and its nuclear signaling
    Kai Prager
    Department of Neurology, University of Bonn, Bonn, Germany
    J Biol Chem 282:14083-93. 2007
    ....
  14. pmc Locus ceruleus controls Alzheimer's disease pathology by modulating microglial functions through norepinephrine
    Michael T Heneka
    Department of Neurology, Deutsches Zentrum für Neurodegenerative Erkrankungen, University of Bonn, 53105 Bonn, Germany
    Proc Natl Acad Sci U S A 107:6058-63. 2010
    ..Consequently, therapies targeting microglial phagocytosis should be tested under NE depletion...
  15. doi request reprint Nitration of tyrosine 10 critically enhances amyloid β aggregation and plaque formation
    Markus P Kummer
    Clinical Neuroscience Unit, Department of Neurology, University of Bonn, Sigmund Freud Strasse 25, 53127 Bonn, Germany
    Neuron 71:833-44. 2011
    ..Further, injection of 3NTyr(10)-Aβ into the brain of young APP/PS1 mice induced β-amyloidosis. This suggests a disease modifying role for NOS2 in AD and therefore represents a potential therapeutic target...
  16. ncbi request reprint Inhibition of glycosphingolipid biosynthesis reduces secretion of the beta-amyloid precursor protein and amyloid beta-peptide
    Irfan Y Tamboli
    Department of Neurology, University of Bonn, Sigmund Freud Strasse 25, 53127 Bonn, Germany
    J Biol Chem 280:28110-7. 2005
    ..Thus, enzymes involved in glycosphingolipid metabolism might represent targets to inhibit the production of amyloid beta-peptides...
  17. doi request reprint Presenilin-1 L166P mutant human pluripotent stem cell-derived neurons exhibit partial loss of γ-secretase activity in endogenous amyloid-β generation
    Philipp Koch
    Institute of Reconstructive Neurobiology, Life and Brain Center, University of Bonn and Hertie Foundation, Bonn, Germany
    Am J Pathol 180:2404-16. 2012
    ..Pluripotent stem cell-derived neurons thus provide experimental access to key steps in AD pathogenesis and can be used to screen pharmaceutical compounds directly in a human neuronal system...
  18. doi request reprint Sphingolipid storage affects autophagic metabolism of the amyloid precursor protein and promotes Abeta generation
    Irfan Y Tamboli
    Department of Neurology, University of Bonn, 53127 Bonn, Germany
    J Neurosci 31:1837-49. 2011
    ..Thus, accumulation of SLs might not only underlie the pathogenesis of LSDs, but also trigger increased generation of Aβ and contribute to neurodegeneration in sporadic AD...
  19. doi request reprint CK2-dependent phosphorylation determines cellular localization and stability of ataxin-3
    Thorsten Mueller
    Department of Neurology, Friedrich Wilhelms University Bonn, UKB, 53105 Bonn, Germany
    Hum Mol Genet 18:3334-43. 2009
    ..Moreover, we found that ATXN3 shifted to the nucleus upon thermal stress in a CK2-dependent manner, indicating a key role of CK2-mediated phosphorylation of ATXN3 in SCA3 pathophysiology...
  20. ncbi request reprint Proteolytic processing of the serine protease matriptase-2: identification of the cleavage sites required for its autocatalytic release from the cell surface
    Marit Stirnberg
    Pharmaceutical Institute, University of Bonn, Germany
    Biochem J 430:87-95. 2010
    ....
  21. doi request reprint Sphingolipids: critical players in Alzheimer's disease
    Gerhild van Echten-Deckert
    Life and Medical Sciences, Membrane Biology and Lipid Biochemistry Unit at the Kekulé Institute, University of Bonn, Gerhard Domagk Str 1, 53121 Bonn, Germany
    Prog Lipid Res 51:378-93. 2012
    ..In recent studies it became evident that impaired sphingolipid metabolism could also be involved in Alzheimer's disease...
  22. doi request reprint Early intraneuronal accumulation and increased aggregation of phosphorylated Abeta in a mouse model of Alzheimer's disease
    Sathish Kumar
    Department of Neurology, University of Bonn, 53127, Bonn, Germany
    Acta Neuropathol 125:699-709. 2013
    ..Thus, phosphorylated Aβ could represent an important species in the formation and stabilization of neurotoxic aggregates, and might be targeted for AD therapy and diagnosis...
  23. doi request reprint Cerebral small vessel disease-induced apolipoprotein E leakage is associated with Alzheimer disease and the accumulation of amyloid beta-protein in perivascular astrocytes
    Sabrina Utter
    Department of Neuropathology, University of Bonn, Bonn, Germany
    J Neuropathol Exp Neurol 67:842-56. 2008
    ..It is therefore tempting to speculate that apoE represents a pathogenetic link between SVD and AD...
  24. ncbi request reprint GGA proteins regulate retrograde transport of BACE1 from endosomes to the trans-Golgi network
    Tina Wahle
    Department of Neurology, Laboratory of Molecular Cell Biology, University of Bonn, Sigmund Freud Str 25, 53127 Bonn, Germany
    Mol Cell Neurosci 29:453-61. 2005
    ..Our data indicate that GGA proteins are not only involved in the sorting at the TGN but also mediate the retrograde transport of cargo proteins from endosomes to the TGN...
  25. pmc Functional relevance of a novel SlyX motif in non-conventional secretion of insulin-degrading enzyme
    Konstantin Glebov
    Department of Neurology, University of Bonn, 53127 Bonn, Germany
    J Biol Chem 286:22711-5. 2011
    ..The combined data indicate that the non-conventional secretion of IDE is regulated by the newly identified SlyX motif...
  26. pmc Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice
    Michael T Heneka
    Department of Neurology, University of Munster, 48149 Munster, Germany
    J Neuroinflammation 2:22. 2005
    ..Transgenic mice overexpressing the london mutant of amyloid precursor protein, APP [V717I], robustly recapitulate the amyloid pathology of AD...
  27. doi request reprint TLR2 is a primary receptor for Alzheimer's amyloid β peptide to trigger neuroinflammatory activation
    Shirong Liu
    Department of Neurology, University of the Saarland, 66421 Homburg Saar, Germany
    J Immunol 188:1098-107. 2012
    ..Our study demonstrated that TLR2 is a primary receptor for Aβ to trigger neuroinflammatory activation and suggested that inhibition of TLR2 in microglia could be beneficial in Alzheimer's disease pathogenesis...
  28. pmc Nonsteroidal anti-inflammatory drugs repress beta-secretase gene promoter activity by the activation of PPARgamma
    Magdalena Sastre
    Department of Neurology, University of Bonn, Sigmund Freud Strasse 25, 53127 Bonn, Germany
    Proc Natl Acad Sci U S A 103:443-8. 2006
    ....
  29. doi request reprint Statins in unconventional secretion of insulin-degrading enzyme and degradation of the amyloid-β peptide
    Konstantin Glebov
    Department of Neurology, University of Bonn, Bonn, Germany
    Neurodegener Dis 10:309-12. 2012
    ..Taken these findings together, the increased clearance of Aβ by stimulated secretion of IDE might contribute to the protective effects of statins against AD...
  30. ncbi request reprint Sphingosine-1-phosphate: boon and bane for the brain
    Gerhild van Echten-Deckert
    Life and Medical Sciences LIMES, Membrane Biology and Lipid Biochemistry Unit at the Kekulé Institute, University of Bonn, Bonn, Germany
    Cell Physiol Biochem 34:148-57. 2014
    ..However, our understanding of the molecular mechanisms that underlie the physiological and pathophysiological actions of S1P in neurons remains rather scarce. © 2014 S. Karger AG, Basel. ..
  31. ncbi request reprint Phosphorylation of presenilin 1 at the caspase recognition site regulates its proteolytic processing and the progression of apoptosis
    Regina Fluhrer
    Department of Neurology, University of Bonn, Sigmund Freud Strasse 25, 53127 Bonn, Germany
    J Biol Chem 279:1585-93. 2004
    ..Moreover, PS1 phosphorylation reduces the progression of apoptosis. Our data indicate that phosphorylation/dephosphorylation at the caspase recognition site provides a mechanism to reversibly regulate properties of PS1 in apoptosis...
  32. pmc RNA aptamers selectively modulate protein recruitment to the cytoplasmic domain of beta-secretase BACE1 in vitro
    Andrea Rentmeister
    LIMES Program Unit Chemical Biology and Medicinal Chemistry, Universitat Bonn, 53121 Bonn, Germany
    RNA 12:1650-60. 2006
    ..Because phosphorylation and GGA1 binding to B1-CT regulate BACE1 transport, these RNA inhibitors could be applied to investigate B1-CT activity without affecting the subcellular localization of BACE1...
  33. ncbi request reprint Down-regulation of endogenous amyloid precursor protein processing due to cellular aging
    Andreas Kern
    Institute for Physiological Chemistry and Pathobiochemistry, Johannes Gutenberg University Mainz, 55099 Mainz, Germany
    J Biol Chem 281:2405-13. 2006
    ..In conclusion, we have found a significant modulation of endogenous APP processing and maturation in human fibroblasts caused by age-associated alterations in cellular biochemistry...
  34. ncbi request reprint Identification of a beta-secretase activity, which truncates amyloid beta-peptide after its presenilin-dependent generation
    Regina Fluhrer
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Schillerstrasse 44, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 278:5531-8. 2003
    ..These data demonstrate that an apparently gamma-secretase-dependent A beta derivative is produced after the generation of the non-truncated A beta via an additional and unexpected activity of BACE...
  35. ncbi request reprint Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an Abeta-like peptide
    Sven Lammich
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 277:44754-9. 2002
    ..The dual cleavage mechanism is required for nuclear signaling as well as removal of remaining transmembrane domains, a general function of PS in membrane protein metabolism...
  36. ncbi request reprint A non-amyloidogenic function of BACE-2 in the secretory pathway
    Regina Fluhrer
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, Munich, Germany
    J Neurochem 81:1011-20. 2002
    ..These data indicate that the distinct specificities of BACE-1 and BACE-2 in their cleavage of betaAPP differentially affect the generation of Abeta...
  37. ncbi request reprint Apical sorting of beta-secretase limits amyloid beta-peptide production
    Anja Capell
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Schillerstrasse 44, Ludwig Maximilians University, Munich 80336, Germany
    J Biol Chem 277:5637-43. 2002
    ..These data demonstrate that Abeta production is limited in polarized cells by differential targeting of BACE and its substrate betaAPP. Moreover, our findings suggest that betaAPP may not be a major physiological substrate of BACE...