Christian Haass

Summary

Affiliation: University of Munich
Country: Germany

Publications

  1. pmc Presenilin-1 affects trafficking and processing of betaAPP and is targeted in a complex with nicastrin to the plasma membrane
    Christoph Kaether
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Cell Biol 158:551-61. 2002
  2. ncbi request reprint Alzheimer disease gamma-secretase: a complex story of GxGD-type presenilin proteases
    Christian Haass
    Adolf Butenandt Institute, Dept of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University Munich, Schillerstr 44, 80336 Munich, Germany
    Trends Cell Biol 12:556-62. 2002
  3. pmc Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes
    Philipp J Kahle
    Laboratory for Alzheimer s and Parkinson s Disease Research, Department of Biochemistry, Ludwig Maximilians University, D 80336 Munich, Germany
    EMBO Rep 3:583-8. 2002
  4. pmc Take five--BACE and the gamma-secretase quartet conduct Alzheimer's amyloid beta-peptide generation
    Christian Haass
    Department of Biochemistry, Adolf Butenandt Institute, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, Munchen, Germany
    EMBO J 23:483-8. 2004
  5. ncbi request reprint The biological and pathological function of presenilin proteins--simple cell systems and a worm in Alzheimer's disease research
    C Haass
    Adolf Butenandt Institute, Ludwig Maximilians University Munich, Dept of Biochemistry, Germany
    Eur Arch Psychiatry Clin Neurosci 249:23-7. 1999
  6. ncbi request reprint The presenilins in Alzheimer's disease--proteolysis holds the key
    C Haass
    Adolf Butenandt Institute, Department of Biochemistry, Ludwig Maximilians University Munich, Germany
    Science 286:916-9. 1999
  7. ncbi request reprint Amyloid precursor-like protein 1 influences endocytosis and proteolytic processing of the amyloid precursor protein
    Stephanie Neumann
    Adolf Butenandt Institut, Ludwig Maximilians University, Schillerstrasse 44, 80336 Munich, Germany
    J Biol Chem 281:7583-94. 2006
  8. ncbi request reprint Gamma-secretase complex assembly within the early secretory pathway
    Anja Capell
    Adolf Butenandt Institut, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians Universitat, Schillerstrasse 44, 80336 Munich, Germany
    J Biol Chem 280:6471-8. 2005
  9. doi request reprint A novel sorting nexin modulates endocytic trafficking and alpha-secretase cleavage of the amyloid precursor protein
    Susanne Schöbel
    Center for Integrated Protein Science and the Adolf Butenandt Institut, Ludwig Maximilians University, Munich, Germany
    J Biol Chem 283:14257-68. 2008
  10. 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

Detail Information

Publications120 found, 100 shown here

  1. pmc Presenilin-1 affects trafficking and processing of betaAPP and is targeted in a complex with nicastrin to the plasma membrane
    Christoph Kaether
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Cell Biol 158:551-61. 2002
    ..Our data suggest that PS is targeted as a biologically active complex with Nct through the secretory pathway to the cell surface and suggest a dual function of PS in gamma-secretase processing and in trafficking...
  2. ncbi request reprint Alzheimer disease gamma-secretase: a complex story of GxGD-type presenilin proteases
    Christian Haass
    Adolf Butenandt Institute, Dept of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University Munich, Schillerstr 44, 80336 Munich, Germany
    Trends Cell Biol 12:556-62. 2002
    ....
  3. pmc Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes
    Philipp J Kahle
    Laboratory for Alzheimer s and Parkinson s Disease Research, Department of Biochemistry, Ludwig Maximilians University, D 80336 Munich, Germany
    EMBO Rep 3:583-8. 2002
    ..Thus, ectopic expression alpha SYN in OLs might initiate salient features of MSA pathology...
  4. pmc Take five--BACE and the gamma-secretase quartet conduct Alzheimer's amyloid beta-peptide generation
    Christian Haass
    Department of Biochemistry, Adolf Butenandt Institute, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, Munchen, Germany
    EMBO J 23:483-8. 2004
    ..It now appears that one needs to Take Five genes to produce a deadly peptide by a proteolytic mechanism, which paradoxically is otherwise of pivotal importance for development and cell fate decisions...
  5. ncbi request reprint The biological and pathological function of presenilin proteins--simple cell systems and a worm in Alzheimer's disease research
    C Haass
    Adolf Butenandt Institute, Ludwig Maximilians University Munich, Dept of Biochemistry, Germany
    Eur Arch Psychiatry Clin Neurosci 249:23-7. 1999
    ..Here we will summarize the pathological as well as biological function of PS and demonstrate that simple systems, such as cultured cells and the worm Caenorhabditis elegans can be used for modern AD research...
  6. ncbi request reprint The presenilins in Alzheimer's disease--proteolysis holds the key
    C Haass
    Adolf Butenandt Institute, Department of Biochemistry, Ludwig Maximilians University Munich, Germany
    Science 286:916-9. 1999
    ..These findings suggest that the presenilins may prove to be valuable molecular targets for the development of drugs to combat AD...
  7. ncbi request reprint Amyloid precursor-like protein 1 influences endocytosis and proteolytic processing of the amyloid precursor protein
    Stephanie Neumann
    Adolf Butenandt Institut, Ludwig Maximilians University, Schillerstrasse 44, 80336 Munich, Germany
    J Biol Chem 281:7583-94. 2006
    ..In summary, our study provides a novel mechanism for APP shedding, in which APLP1 affects the endocytosis of APP and makes more APP available for alpha-secretase cleavage...
  8. ncbi request reprint Gamma-secretase complex assembly within the early secretory pathway
    Anja Capell
    Adolf Butenandt Institut, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians Universitat, Schillerstrasse 44, 80336 Munich, Germany
    J Biol Chem 280:6471-8. 2005
    ....
  9. doi request reprint A novel sorting nexin modulates endocytic trafficking and alpha-secretase cleavage of the amyloid precursor protein
    Susanne Schöbel
    Center for Integrated Protein Science and the Adolf Butenandt Institut, Ludwig Maximilians University, Munich, Germany
    J Biol Chem 283:14257-68. 2008
    ....
  10. 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...
  11. ncbi request reprint The GxGD motif of presenilin contributes to catalytic function and substrate identification of gamma-secretase
    Aya Yamasaki
    Laboratory for Alzheimer s and Parkinson s Disease Research, Department of Biochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany
    J Neurosci 26:3821-8. 2006
    ..Our data thus implicate a role of the GxGD motif in catalytic function and substrate identification of gamma-secretase...
  12. ncbi request reprint Reconstitution of gamma-secretase activity
    Dieter Edbauer
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Nat Cell Biol 5:486-8. 2003
    ..Thus, the biological activity of gamma-secretase is reconstituted by the co-expression of human PS, Nct, APH-1 and PEN-2 in yeast...
  13. ncbi request reprint Immature nicastrin stabilizes APH-1 independent of PEN-2 and presenilin: identification of nicastrin mutants that selectively interact with APH-1
    Keiro Shirotani
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Neurochem 89:1520-7. 2004
    ..Moreover, binding of the latter two complex partners critically depends on the integrity of the Nct ectodomain...
  14. ncbi request reprint Differential localization and identification of a critical aspartate suggest non-redundant proteolytic functions of the presenilin homologues SPPL2b and SPPL3
    Peter Krawitz
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, Schillerstrasse 44, 80336 Munich, Germany
    J Biol Chem 280:39515-23. 2005
    ..Furthermore, SPPL2b is shown to be the first member of the SPP/PSH/SPPL family that is not located within the ER but in endosomal/lysosomal vesicles...
  15. ncbi request reprint Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b
    Lucas Martin
    Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 283:1644-52. 2008
    ....
  16. ncbi request reprint Substrate requirements for SPPL2b-dependent regulated intramembrane proteolysis
    Lucas Martin
    Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 284:5662-70. 2009
    ....
  17. ncbi request reprint Nicastrin interacts with gamma-secretase complex components via the N-terminal part of its transmembrane domain
    Anja Capell
    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 278:52519-23. 2003
    ..We identified the N-terminal region of the NCT TMD as a functionally important entity of NCT. These data thus demonstrate that NCT interacts with other gamma-secretase complex components via its TMD...
  18. 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...
  19. pmc Intramembrane proteolysis of GXGD-type aspartyl proteases is slowed by a familial Alzheimer disease-like mutation
    Regina Fluhrer
    Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Ludwig Maximilians University, Munich 80336, Germany
    J Biol Chem 283:30121-8. 2008
    ..Thus, the PS1 G384A mutation causes a selective loss of function by slowing the processing pathway leading to the benign Abeta40...
  20. 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...
  21. ncbi request reprint Structural determinants of the C-terminal helix-kink-helix motif essential for protein stability and survival promoting activity of DJ-1
    Karin Görner
    Laboratory of Alzheimer s and Parkinson s Disease Research, Department of Biochemistry, Ludwig Maximilians University of Munich, 80336 Munich, Germany
    J Biol Chem 282:13680-91. 2007
    ....
  22. ncbi request reprint Identification of distinct gamma-secretase complexes with different APH-1 variants
    Keiro Shirotani
    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 279:41340-5. 2004
    ..Taken together, our results suggest that, dependent on the tissue expression of the individual subunits, six distinct gamma-secretase complexes composed of the known subunits can exist in human cells...
  23. ncbi request reprint Dimerization of beta-site beta-amyloid precursor protein-cleaving enzyme
    Gil G Westmeyer
    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 279:53205-12. 2004
    ..Dimerization of BACE might, thus, facilitate binding and cleavage of physiological substrates...
  24. ncbi request reprint Missense mutations in the progranulin gene linked to frontotemporal lobar degeneration with ubiquitin-immunoreactive inclusions reduce progranulin production and secretion
    Sunita S Shankaran
    Munich Center for Integrated Protein Science and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Schillerstrasse 44, 80336 Munich, Germany
    J Biol Chem 283:1744-53. 2008
    ..Upon reduction of progranulin, neither a major redistribution of TDP-43 nor proteolytic processing to disease-characterizing C-terminal fragments could be observed...
  25. pmc Inhibition of mitochondrial fusion by α-synuclein is rescued by PINK1, Parkin and DJ-1
    Frits Kamp
    DZNE German Center for Neurodegenerative Diseases, Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, Munich, Germany
    EMBO J 29:3571-89. 2010
    ..Finally, mitochondrial fragmentation induced by expression of αS is rescued by coexpression of PINK1, parkin or DJ-1 but not the PD-associated mutations PINK1 G309D and parkin Δ1-79 or by DJ-1 C106A...
  26. pmc Transmembrane protein 147 (TMEM147) is a novel component of the Nicalin-NOMO protein complex
    Ulf Dettmer
    German Center for Neurodegenerative Diseases DZNE and the Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, D 80336 Munich, Germany
    J Biol Chem 285:26174-81. 2010
    ..We conclude that TMEM147 is a novel core component of the Nicalin-NOMO complex, further emphasizing its similarity with gamma-secretase...
  27. ncbi request reprint PEN-2 is an integral component of the gamma-secretase complex required for coordinated expression of presenilin and nicastrin
    Harald Steiner
    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 277:39062-5. 2002
    ..We conclude that PEN-2 is an integral gamma-secretase complex component and that gamma-secretase complex components are expressed in a coordinated manner...
  28. doi request reprint Dual cleavage of neuregulin 1 type III by BACE1 and ADAM17 liberates its EGF-like domain and allows paracrine signaling
    Daniel Fleck
    Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, 80336 Munich, Germany
    J Neurosci 33:7856-69. 2013
    ..Our data suggest that NRG1 type III-dependent myelination is not only controlled by membrane-retained NRG1 type III, but also in a paracrine manner via proteolytic liberation of the EGF-like domain...
  29. pmc The presenilin C-terminus is required for ER-retention, nicastrin-binding and gamma-secretase activity
    Christoph Kaether
    Laboratory for Alzheimer s and Parkinson s Disease Research, Department of Biochemistry, Adolf Butenandt Institute, Ludwig Maximilians Universitat, Munchen, Germany
    EMBO J 23:4738-48. 2004
    ..Deletion of the retention signal results in the release of PS1 from the ER and the assembly of a nonfunctional gamma-secretase complex, suggesting that at least a part of the retention motif may also be required for the function of PS1...
  30. pmc Membrane orientation and subcellular localization of transmembrane protein 106B (TMEM106B), a major risk factor for frontotemporal lobar degeneration
    Christina M Lang
    Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 287:19355-65. 2012
    ..Our findings provide a biochemical and cell biological basis for the understanding of the pathological role of TMEM106B in FTLD, an incurable neurodegenerative disorder...
  31. pmc Parkin is protective against proteotoxic stress in a transgenic zebrafish model
    Mareike E Fett
    Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany
    PLoS ONE 5:e11783. 2010
    ..In order to study the function of parkin in more detail and to address possible differences in its role in different species, we chose Danio rerio as a different vertebrate model system...
  32. ncbi request reprint Amyloid precursor protein and Notch intracellular domains are generated after transport of their precursors to the cell surface
    Christoph Kaether
    Department of Biochemistry, Adolf Butenandt Institute, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munchen, Germany
    Traffic 7:408-15. 2006
    ..Similar results were obtained for another gamma-secretase substrate, NotchDeltaE. Our results suggest that intracellular domains are generated by gamma-secretase at the plasma membrane and/or early endosomes...
  33. doi request reprint Rescue of progranulin deficiency associated with frontotemporal lobar degeneration by alkalizing reagents and inhibition of vacuolar ATPase
    Anja Capell
    German Center for Neurodegenerative Diseases, Ludwig Maximilians University, 80336 Munich, Germany
    J Neurosci 31:1885-94. 2011
    ..Thus, alkalizing reagents, specifically those already used in humans for other applications, and vacuolar ATPase inhibitors may be therapeutically used to prevent GRN-dependent neurodegeneration...
  34. doi request reprint Important functional role of residue x of the presenilin GxGD protease active site motif for APP substrate cleavage specificity and substrate selectivity of γ-secretase
    Benedikt Kretner
    Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, Munich, Germany
    J Neurochem 125:144-56. 2013
    ..We suggest that L383 and the flanking glycine residues form a spatial arrangement in PS1 that is critical for docking and/or cleavage of different γ-secretase substrates...
  35. pmc The α-helical content of the transmembrane domain of the British dementia protein-2 (Bri2) determines its processing by signal peptide peptidase-like 2b (SPPL2b)
    Regina Fluhrer
    Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University Munich, 80336 Munich, Germany
    J Biol Chem 287:5156-63. 2012
    ..Other glycine residues do not influence the α-helical content of the transmembrane domain nor its intramembrane processing...
  36. pmc Expression of the anti-amyloidogenic secretase ADAM10 is suppressed by its 5'-untranslated region
    Sven Lammich
    German Center for Neurodegenerative Diseases DZNE and Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 285:15753-60. 2010
    ..Thus, we provide evidence that the 5'-UTR of ADAM10 may have an important role for post-transcriptional regulation of ADAM10 expression and consequently Abeta production...
  37. doi request reprint Requirement for small side chain residues within the GxGD-motif of presenilin for gamma-secretase substrate cleavage
    Blanca Isabel Pérez-Revuelta
    Deutsches Zentrum für Neurodegenerative Erkrankungen DZNE and Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, Munchen, Germany
    J Neurochem 112:940-50. 2010
    ..These findings broaden our understanding of gamma-secretase substrate recognition and cleavage, which may prove crucial for therapeutic targeting of the enzyme...
  38. ncbi request reprint Purification, pharmacological modulation, and biochemical characterization of interactors of endogenous human gamma-secretase
    Edith Winkler
    Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Biochemistry 48:1183-97. 2009
    ..In addition, we provide evidence that the copurifying proteins identified are unlikely to be part of the active gamma-secretase enzyme...
  39. ncbi request reprint Length and overall sequence of the PEN-2 C-terminal domain determines its function in the stabilization of presenilin fragments
    Stefan Prokop
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, Munich, Germany
    J Neurochem 94:57-62. 2005
    ..Taken together, our data suggest that the PS-subunit stabilizing function of PEN-2 depends on length and overall sequence of its C-terminal domain...
  40. ncbi request reprint The Nicastrin-like protein Nicalin regulates assembly and stability of the Nicalin-nodal modulator (NOMO) membrane protein complex
    Christof Haffner
    Center of Integrated Protein Science and the Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Ludwig Maximilians University, D 80336 Munich, Germany
    J Biol Chem 282:10632-8. 2007
    ..In contrast, Nicalin levels are limited independently of NOMO. We, therefore, propose that Nicalin controls the assembly and stability of the Nicalin-NOMO complex...
  41. ncbi request reprint Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins
    Kohji Mori
    Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University Munich, Schillerstr 44, 80336, Munich, Germany
    Acta Neuropathol 126:881-93. 2013
    ..Novel monoclonal antibodies against poly-(Gly-Arg) will facilitate pathological diagnosis of C9orf72 FTLD/ALS...
  42. doi request reprint The Nicastrin ectodomain adopts a highly thermostable structure
    Regina Fluhrer
    Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, Schillerstrasse 44, 80336 Munich, Germany
    Biol Chem 392:995-1001. 2011
    ..These findings provide evidence to further support the hypothesis that Nicastrin may share evolutionary conserved properties with the aminopeptidase and the transferrin receptor family...
  43. ncbi request reprint Control of peripheral nerve myelination by the beta-secretase BACE1
    Michael Willem
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Schillerstrasse 44, Ludwig Maximilians University, 80336 Munich, Germany
    Science 314:664-6. 2006
    ..Thus, BACE1 is required for myelination and correct bundling of axons by Schwann cells, probably through processing of type III NRG1...
  44. pmc Beta-amyloid precursor protein mutants respond to gamma-secretase modulators
    Richard M Page
    German Center for Neurodegenerative Diseases DZNE and Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 285:17798-810. 2010
    ....
  45. ncbi request reprint Methylene blue fails to inhibit Tau and polyglutamine protein dependent toxicity in zebrafish
    Frauke van Bebber
    German Center for Neurodegenerative Diseases DZNE and Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, Schillerstr 44, Munich, Germany
    Neurobiol Dis 39:265-71. 2010
    ..Our findings are consistent with the hypothesis that toxicity is not necessarily associated with deposition of insoluble amyloid proteins...
  46. pmc Endoplasmic reticulum retention of the gamma-secretase complex component Pen2 by Rer1
    Christoph Kaether
    Laboratory for Alzheimer s and Parkinson s Disease Research, Department of Biochemistry, Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Ludwig Maximilians Universitat, München 80336, Germany
    EMBO Rep 8:743-8. 2007
    ..To our knowledge, Rer1 is the first identified interaction partner of mammalian transmembrane-based retention/retrieval signals...
  47. ncbi request reprint Regulated intramembrane proteolysis of the interleukin-1 receptor II by alpha-, beta-, and gamma-secretase
    Peer Hendrik Kuhn
    Adolf Butenandt Institut, Ludwig Maximilians University, Schillerstrasse 44, 80336 Munich, Germany
    J Biol Chem 282:11982-95. 2007
    ..This study reveals a similar proteolytic processing of IL-1R2 and APP and may provide an explanation for the increased IL-1R2 secretion observed in AD...
  48. ncbi request reprint Pathological activity of familial Alzheimer's disease-associated mutant presenilin can be executed by six different gamma-secretase complexes
    Keiro Shirotani
    Munich Center for Integrated Protein Science and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, Schillerstr 44, Munich, Germany
    Neurobiol Dis 27:102-7. 2007
    ....
  49. pmc Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formation
    Dieter Edbauer
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Schillerstrasse 44, Ludwig Maximilians University, 80336 Munich, Germany
    Proc Natl Acad Sci U S A 99:8666-71. 2002
    ..Based on these findings we conclude that Nct and PS regulate each other and determine gamma-secretase function via complex formation...
  50. pmc Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production
    Tobias Moehlmann
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Proc Natl Acad Sci U S A 99:8025-30. 2002
    ..Finally, we show that PS1 L166 mutants affect the generation of NICD and AICD in a similar manner, supporting the concept that S3 protease and S3-like gamma-secretase cleavages are mediated by identical proteolytic activities...
  51. ncbi request reprint Generation of Abeta38 and Abeta42 is independently and differentially affected by familial Alzheimer disease-associated presenilin mutations and gamma-secretase modulation
    Richard M Page
    Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 283:677-83. 2008
    ..Furthermore, human patients with certain PS mutations may not respond to gamma-secretase modulators...
  52. doi request reprint The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS
    Kohji Mori
    Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University LMU Munich, Munich, Germany
    Science 339:1335-8. 2013
    ..These findings directly link the FTLD/ALS-associated genetic mutation to the predominant pathology in patients with C9orf72 hexanucleotide expansion...
  53. ncbi request reprint Regional distribution of proteinase K-resistant alpha-synuclein correlates with Lewy body disease stage
    Manuela Neumann
    Institute of Neuropathology, Laboratory of Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, Munich, Germany
    J Neuropathol Exp Neurol 63:1225-35. 2004
    ..Variable amounts of neuritic PK-resistant alphaSYN were found in the striatum of all cases. Thus, PK resistance of alphaSYN may be useful for the development of biomarkers of LB diseases...
  54. pmc Loss of ALS-associated TDP-43 in zebrafish causes muscle degeneration, vascular dysfunction, and reduced motor neuron axon outgrowth
    Bettina Schmid
    German Center for Neurodegenerative Diseases, 80336 Munich, Germany
    Proc Natl Acad Sci U S A 110:4986-91. 2013
    ..Strikingly, Filamin C is similarly increased in the frontal cortex of FTLD-TDP patients, suggesting aberrant expression in smooth muscle cells and TDP-43 loss-of-function as one underlying disease mechanism...
  55. ncbi request reprint hnRNP A3 binds to GGGGCC repeats and is a constituent of p62-positive/TDP43-negative inclusions in the hippocampus of patients with C9orf72 mutations
    Kohji Mori
    Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, Schillerstr 44, 80336, Munich, Germany
    Acta Neuropathol 125:413-23. 2013
    ..Thus, we have identified one protein component of these pathognomonic inclusions...
  56. pmc Arginine methylation next to the PY-NLS modulates Transportin binding and nuclear import of FUS
    Dorothee Dormann
    Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, Munich, Germany
    EMBO J 31:4258-75. 2012
    ....
  57. pmc Requirements for stress granule recruitment of fused in sarcoma (FUS) and TAR DNA-binding protein of 43 kDa (TDP-43)
    Eva Bentmann
    Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, Munchen, Germany
    J Biol Chem 287:23079-94. 2012
    ....
  58. pmc Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation
    A Kathrin Lutz
    Neurobiochemistry, Deutsches Zentrum für Neurodegenerative Erkrankungen and Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 284:22938-51. 2009
    ..We propose that the discrepant findings in adult flies can be explained by the time of phenotype analysis and suggest that in mammals different strategies may have evolved to cope with dysfunctional mitochondria...
  59. ncbi request reprint Differential effects of Parkinson's disease-associated mutations on stability and folding of DJ-1
    Karin Görner
    Laboratory of Alzheimer s and Parkinson s Disease Research, Department of Biochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 279:6943-51. 2004
    ..Thus, structural defects of [E64D]DJ-1 only become apparent upon denaturing conditions, whereas the L166P mutation causes a drastic defect that leads to excessive degradation...
  60. pmc Intramembrane proteolysis by gamma-secretase
    Harald Steiner
    Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 283:29627-31. 2008
    ..Modulators of gamma-secretase, which selectively affect the production of the pathological 42-amino acid Abeta, do not inhibit Notch signaling...
  61. ncbi request reprint Alpha-synuclein has a high affinity for packing defects in a bilayer membrane: a thermodynamics study
    Brigitte Nuscher
    Department of Biochemistry, Ludwig Maximilian University, 80336 Munich, Germany
    J Biol Chem 279:21966-75. 2004
    ..This will be discussed with regard to a possible role of the protein for the stabilization of synaptic vesicle membranes...
  62. ncbi request reprint Parkin phosphorylation and modulation of its E3 ubiquitin ligase activity
    Ayako Yamamoto
    Laboratory of Alzheimer s and Parkinson s Disease Research, Department of Metabolic Biochemistry, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 280:3390-9. 2005
    ..Thus, complex regulation of the phosphorylation state of parkin may contribute to the unfolded protein response in stressed cells...
  63. pmc Translational repression of the disintegrin and metalloprotease ADAM10 by a stable G-quadruplex secondary structure in its 5'-untranslated region
    Sven Lammich
    Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 286:45063-72. 2011
    ..Thus, we identified a critical RNA secondary structure within the 5'-UTR, which contributes to the translational repression of ADAM10...
  64. pmc Nicalin and its binding partner Nomo are novel Nodal signaling antagonists
    Christof Haffner
    Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany
    EMBO J 23:3041-50. 2004
    ..Our data demonstrate that the Nicalin/Nomo complex antagonizes Nodal signaling during mesendodermal patterning in zebrafish...
  65. ncbi request reprint A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b
    Regina Fluhrer
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Nat Cell Biol 8:894-6. 2006
    ..These findings suggest common principles for regulated intramembrane proteolysis by GxGD aspartyl proteases...
  66. ncbi request reprint Cellular functions of gamma-secretase-related proteins
    Christof Haffner
    Laboratory for Alzheimer s and Parkinson s Disease Research, Department of Biochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany
    Neurodegener Dis 3:284-9. 2006
    ..We found that during zebrafish embryogenesis this complex is involved in the patterning of the axial mesendoderm, a process controlled by the Nodal signaling pathway...
  67. doi request reprint Bepridil and amiodarone simultaneously target the Alzheimer's disease beta- and gamma-secretase via distinct mechanisms
    Stefan Mitterreiter
    German Center for Neurodegenerative Diseases Munich and Adolf Butenandt Institute, Biochemistry, University of Munich, 80336 Munich, Germany
    J Neurosci 30:8974-83. 2010
    ..In addition to Alzheimer's disease, compounds with dual properties may also be useful for drug development targeting other membrane proteins...
  68. pmc Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies
    Manuela Neumann
    Department of Neuropathology, Ludwig Maximilians University, Munich, Germany
    J Clin Invest 110:1429-39. 2002
    ..The transgenic mice showed a progressive deterioration of locomotor function. Thus, misfolding and hyperphosphorylation of alphaS may cause dysfunction of affected brain regions...
  69. ncbi request reprint Requirement of PEN-2 for stabilization of the presenilin N-/C-terminal fragment heterodimer within the gamma-secretase complex
    Stefan Prokop
    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 279:23255-61. 2004
    ..This function critically depends on the PEN-2 C terminus. Moreover, our data show that PEN-2 is generally required for gamma-secretase complex maturation independent of its activity in PS1 endoproteolysis...
  70. ncbi request reprint Co-expression of nicastrin and presenilin rescues a loss of function mutant of APH-1
    Dieter Edbauer
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Schillerstr 44, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 279:37311-5. 2004
    ..We conclude that cooperative effects may stabilize a trim-eric complex of APH-1a G122D together with PS1 and NCT. Upon successful complex assembly, the GXXXG motif becomes dispensable for gamma-secretase activity...
  71. pmc Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease
    Martin Fuhrmann
    Center of Neuropathology and Prion Research, Ludwig Maximilians University, Munich, Germany
    Nat Neurosci 13:411-3. 2010
    ..Knockout of the microglial chemokine receptor Cx3cr1, which is critical in neuron-microglia communication, prevented neuron loss...
  72. pmc Chemical cross-linking provides a model of the gamma-secretase complex subunit architecture and evidence for close proximity of the C-terminal fragment of presenilin with APH-1
    Harald Steiner
    Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 283:34677-86. 2008
    ....
  73. ncbi request reprint Proteolytic processing of TAR DNA binding protein-43 by caspases produces C-terminal fragments with disease defining properties independent of progranulin
    Dorothee Dormann
    Deutsches Zentrum für Neurodegenerative Erkrankungen and Adolf Butenandt Institute, Department of Biochemistry, Ludwig Maximilians University, Munich, Germany
    J Neurochem 110:1082-94. 2009
    ..Our findings therefore suggest that caspase-mediated processing generates CTFs of similar biochemical properties as those occurring in nuclear and cytoplasmic deposits of FTLD-U patients independent of PGRN levels...
  74. ncbi request reprint Amyloid precursor protein intracellular domain modulates cellular calcium homeostasis and ATP content
    Runa Hamid
    Zentrum für Neuropathologie und Prion Forschung, Ludwig Maximilians Universitat, Munchen, Germany
    J Neurochem 102:1264-75. 2007
    ..Based on these observations, our findings indicate that alterations observed in endoplasmic reticulum Ca(2+) storage in cells with reduced amounts of AICD are reciprocally linked to mitochondrial bioenergetic function...
  75. 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...
  76. ncbi request reprint Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein
    M Okochi
    Adolf Butenandt Institute, Department of Biochemistry, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 275:390-7. 2000
    ..These data demonstrate that alpha-synuclein is constitutively phosphorylated within its C terminus and may indicate that the function of alpha-synuclein is regulated by phosphorylation/dephosphorylation...
  77. ncbi request reprint Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin
    Nicole Exner
    Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Neurosci 27:12413-8. 2007
    ..Our results may therefore suggest that PINK1 deficiency in humans results in mitochondrial abnormalities associated with cellular stress, a pathological phenotype, which can be ameliorated by enhanced expression of parkin...
  78. ncbi request reprint Gamma-secretase activity is associated with a conformational change of nicastrin
    Keiro Shirotani
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, Schillerstrasse 44, 80336 Munich, Germany
    J Biol Chem 278:16474-7. 2003
    ..Furthermore, the conformational alteration did not occur in the absence of PS. Our data thus suggest that gamma-secretase function critically depends on the structural "activation" of Nct...
  79. ncbi request reprint Endoproteolysis of the ER stress transducer ATF6 in the presence of functionally inactive presenilins
    H Steiner
    Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Adolf-Butenandt-Institute, Ludwig-Maximilians-University, 80036 Munich, Germany
    Neurobiol Dis 8:717-22. 2001
    ..This finding indicates that gamma-secretase inhibitors, which are currently developed as therapeutic agents to lower the A beta burden in brains of AD patients, do not interfere with the UPR response...
  80. pmc Expression of the Alzheimer protease BACE1 is suppressed via its 5'-untranslated region
    Sven Lammich
    Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Adolf Butenandt Institute, Ludwig Maximilians University, Schillerstrasse 44, 80336 Munich, Germany
    EMBO Rep 5:620-5. 2004
    ..Our data therefore demonstrate translational repression as a new mechanism controlling BACE1 expression...
  81. pmc Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch
    M Sastre
    Adolf Butenandt-Institute, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Ludwig-Maximilians-University, Schillerstrasse 44, 80336 Munich, Germany
    EMBO Rep 2:835-41. 2001
    ..Sequence analysis revealed that CTFgamma is produced by a novel gamma-secretase cut, which occurs at a site corresponding to the S3 cleavage of Notch...
  82. pmc Separation of presenilin function in amyloid beta-peptide generation and endoproteolysis of Notch
    L Kulic
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Proc Natl Acad Sci U S A 97:5913-8. 2000
    ..These results demonstrate that the biological function of PS proteins in the endoproteolysis of beta-amyloid precursor protein and Notch can be separated...
  83. doi request reprint Function, regulation and therapeutic properties of beta-secretase (BACE1)
    Michael Willem
    Center for Integrated Protein Science Munich, Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Semin Cell Dev Biol 20:175-82. 2009
    ..BACE1 is a primary target for Abeta lowering therapies, however the development of high affinity bio-available inhibitors has been a major challenge so far...
  84. doi request reprint Mitochondrial dysfunction in Parkinson's disease
    Konstanze F Winklhofer
    German Center for Neurodegenerative Diseases DZNE Munich and Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, Schillerstr 44, D 80336 Munich, Germany
    Biochim Biophys Acta 1802:29-44. 2010
    ..In fact, sporadic and familial PD seem to converge at the level of mitochondrial integrity...
  85. ncbi request reprint The cell adhesion protein P-selectin glycoprotein ligand-1 is a substrate for the aspartyl protease BACE1
    Stefan F Lichtenthaler
    Massachusetts General Hospital Harvard Medical School, Department of Molecular Biology, Boston, Massachusetts 02114, USA
    J Biol Chem 278:48713-9. 2003
    ..The cleavage occurred at a Leu-Ser peptide bond as identified by mass spectrometry using a synthetic peptide. We conclude that PSGL-1 is an additional substrate for BACE1...
  86. ncbi request reprint Single particle detection and characterization of synuclein co-aggregation
    Armin Giese
    Center for Neuropathology and Prion Research, LMU, Munich, Germany
    Biochem Biophys Res Commun 333:1202-10. 2005
    ....
  87. doi request reprint Initiation and propagation of neurodegeneration
    Christian Haass
    DZNE German Center for Neurodegenerative Diseases, Munich, Germany
    Nat Med 16:1201-4. 2010
    ..Is this skepticism misplaced, or do the words of Sir Isaac Newton hold true, that "what we know is a drop, what we don't know is an ocean"?..
  88. pmc A lipid boundary separates APP and secretases and limits amyloid beta-peptide generation
    Christoph Kaether
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilans University, Munchen, Germany
    J Cell Biol 167:809-12. 2004
    ..These findings describe a novel mechanism for controlling proteolytic activity by building a lipid boundary between proteases and their substrates...
  89. pmc How does parkin ligate ubiquitin to Parkinson's disease?
    Philipp J Kahle
    Laboratory of Alzheimer s and Parkinson s Disease Research, Department of Biochemistry, Ludwig Maximilians University of Munich, Schillerstrasse 44, 80336 Munchen, Germany
    EMBO Rep 5:681-5. 2004
    ..The risk factors that predispose dopaminergic neurons to degenerate on parkin failure are yet to be identified...
  90. ncbi request reprint Structure/function of alpha-synuclein in health and disease: rational development of animal models for Parkinson's and related diseases
    Philipp J Kahle
    Department of Biochemistry, Ludwig Maximilians University, Munich, Germany
    J Neurochem 82:449-57. 2002
  91. ncbi request reprint Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide
    Christian Haass
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Nat Rev Mol Cell Biol 8:101-12. 2007
    ..Findings in other neurodegenerative diseases indicate that a broadly similar process of neuronal dysfunction is induced by diffusible oligomers of misfolded proteins...
  92. ncbi request reprint The biochemical and genetic odyssey to the function of a nicastrin-like protein
    Christof Haffner
    Laboratory for Alzheimer s and Parkinson s Disease Research, Department of Biochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany
    Neurodegener Dis 1:192-5. 2004
    ..Thus, nicastrin and nicalin are both associated with protein complexes involved in cell fate decisions during early embryonic development...
  93. ncbi request reprint Pore-forming scissors? A first structural glimpse of gamma-secretase
    Harald Steiner
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, Schillerstrasse 44, 80336 Munich, Germany
    Trends Biochem Sci 31:491-3. 2006
    ..It indicates a spherical transmembrane particle with an interior chamber that, presumably, accommodates its catalytic residues, and two openings that might be exit sites for the cleavage products...
  94. ncbi request reprint Phosphorylation regulates intracellular trafficking of beta-secretase
    J Walter
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 44 Schillerstrasse, 80336 Munich, Germany
    J Biol Chem 276:14634-41. 2001
    ..In contrast, nonphosphorylatable BACE S498A is retained within early endosomes. Our results therefore demonstrate regulated trafficking of BACE within the secretory and endocytic pathway...
  95. ncbi request reprint Maturation and pro-peptide cleavage of beta-secretase
    A Capell
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 275:30849-54. 2000
    ..Pro-BACE was predominantly located within the endoplasmic reticulum. Pro-peptide cleavage occurred immediately before full maturation and trafficking through the Golgi...
  96. ncbi request reprint Phosphorylation of the beta-amyloid precursor protein at the cell surface by ectocasein kinases 1 and 2
    J Walter
    Adolf Butenandt Institut, Department of Biochemistry, Laboratory for Alzheimer s Disease Research, Ludwig Maximilians Universät München, Schillerstrasse 44, D 80336 Munich, Germany
    J Biol Chem 275:23523-9. 2000
    ..Heparin strongly inhibited the phosphorylation of cell-surface betaAPP by ecto-CK1 and ecto-CK2, indicating a regulatory role of this extracellular matrix component in betaAPP phosphorylation...
  97. ncbi request reprint Subcellular localization of wild-type and Parkinson's disease-associated mutant alpha -synuclein in human and transgenic mouse brain
    P J Kahle
    Adolf Butenandt Institute, Department of Biochemistry, Ludwig Maximilians University, 80336 Munich, Germany
    J Neurosci 20:6365-73. 2000
    ..Thus, mutant [A30P]alphaSYN does not fail to be transported to synapses, but its transgenic overexpression apparently leads to abnormal cellular accumulations...
  98. ncbi request reprint A pathogenic presenilin-1 deletion causes abberrant Abeta 42 production in the absence of congophilic amyloid plaques
    H Steiner
    Adolf Butenandt-Institute, Department of Biochemistry, Laboratory for Alzheimer's Disease Research, Ludwig-Maximilians-University, 80336 Munich, Germany
    J Biol Chem 276:7233-9. 2001
    ..Since increased Abeta42 production is not associated with classical senile plaque formation, these data demonstrate that amyloid plaque formation is not a prerequisite for dementia and neurodegeneration...
  99. ncbi request reprint Physiology and pathophysiology of alpha-synuclein. Cell culture and transgenic animal models based on a Parkinson's disease-associated protein
    P J Kahle
    Adolf Butenandt Institute, Department of Biochemistry, Ludwig Maximilians University, Schillerstrasse 44, 80336 Munich, Germany
    Ann N Y Acad Sci 920:33-41. 2000
    ..Thus, Parkinson's disease-associated mutations might perturb axonal transport, leading to somal accumulation of alpha-SYN and eventually Lewy body formation...
  100. ncbi request reprint Nuclear signaling: a common function of presenilin substrates?
    H Steiner
    Adolf Butenandt lnstitute, Department of Biochemistry, Ludwig Maximilians University, Munich, Germany
    J Mol Neurosci 17:193-8. 2001
    ..In this review we will discuss a novel putative function of betaAPP in nuclear signaling, an activity, that betaAPP may share with other presenilin substrates such as Notch...
  101. pmc Selective insolubility of alpha-synuclein in human Lewy body diseases is recapitulated in a transgenic mouse model
    P J Kahle
    Laboratory for Alzheimer s and Parkinson s Disease Research, The Department of Biochemistry, Ludwig Maximilians University, Munich, Germany
    Am J Pathol 159:2215-25. 2001
    ..In conclusion, the specific accumulation of detergent-insoluble alpha-SYN in transgenic mice recapitulates a pivotal feature of human LB diseases...