Research Topics
Genomes and Genes
| Christian HaassSummaryAffiliation: University of Munich Country: Germany Publications
| Collaborators
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Detail Information
Publications
Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytesPhilipp 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...- Alzheimer disease gamma-secretase: a complex story of GxGD-type presenilin proteasesChristian 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.... - Take five--BACE and the gamma-secretase quartet conduct Alzheimer's amyloid beta-peptide generationChristian 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... - The biological and pathological function of presenilin proteins--simple cell systems and a worm in Alzheimer's disease researchC 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... - The presenilins in Alzheimer's disease--proteolysis holds the keyC 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... - Amyloid precursor-like protein 1 influences endocytosis and proteolytic processing of the amyloid precursor proteinStephanie 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... - A novel sorting nexin modulates endocytic trafficking and alpha-secretase cleavage of the amyloid precursor proteinSusanne Schöbel
Center for Integrated Protein Science and the Adolf Butenandt Institut, Ludwig Maximilians University, Munich, Germany
J Biol Chem 283:14257-68. 2008.... - Gamma-secretase complex assembly within the early secretory pathwayAnja 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.... - Reconstitution of gamma-secretase activityDieter 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... - The GxGD motif of presenilin contributes to catalytic function and substrate identification of gamma-secretaseAya 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... - Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an Abeta-like peptideSven 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... - Differential localization and identification of a critical aspartate suggest non-redundant proteolytic functions of the presenilin homologues SPPL2b and SPPL3Peter 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... - Presenilin-1 affects trafficking and processing of betaAPP and is targeted in a complex with nicastrin to the plasma membraneChristoph 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... - Immature nicastrin stabilizes APH-1 independent of PEN-2 and presenilin: identification of nicastrin mutants that selectively interact with APH-1Keiro 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... - Identification of a beta-secretase activity, which truncates amyloid beta-peptide after its presenilin-dependent generationRegina 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... - Nicastrin interacts with gamma-secretase complex components via the N-terminal part of its transmembrane domainAnja 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... - Intramembrane proteolysis of GXGD-type aspartyl proteases is slowed by a familial Alzheimer disease-like mutationRegina 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... - Substrate requirements for SPPL2b-dependent regulated intramembrane proteolysisLucas 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.... - Missense mutations in the progranulin gene linked to frontotemporal lobar degeneration with ubiquitin-immunoreactive inclusions reduce progranulin production and secretionSunita 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... - Transmembrane protein 147 (TMEM147) is a novel component of the Nicalin-NOMO protein complexUlf 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... - Inhibition of mitochondrial fusion by α-synuclein is rescued by PINK1, Parkin and DJ-1Frits 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... - PEN-2 is an integral component of the gamma-secretase complex required for coordinated expression of presenilin and nicastrinHarald 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... - Identification of distinct gamma-secretase complexes with different APH-1 variantsKeiro 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... - Dimerization of beta-site beta-amyloid precursor protein-cleaving enzymeGil 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... - Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2bLucas 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.... - A non-amyloidogenic function of BACE-2 in the secretory pathwayRegina 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... - Structural determinants of the C-terminal helix-kink-helix motif essential for protein stability and survival promoting activity of DJ-1Karin 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.... - The presenilin C-terminus is required for ER-retention, nicastrin-binding and gamma-secretase activityChristoph 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... - Parkin is protective against proteotoxic stress in a transgenic zebrafish modelMareike 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... - Amyloid precursor protein and Notch intracellular domains are generated after transport of their precursors to the cell surfaceChristoph 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... - Rescue of progranulin deficiency associated with frontotemporal lobar degeneration by alkalizing reagents and inhibition of vacuolar ATPaseAnja 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... - The Nicastrin-like protein Nicalin regulates assembly and stability of the Nicalin-nodal modulator (NOMO) membrane protein complexChristof 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... - Length and overall sequence of the PEN-2 C-terminal domain determines its function in the stabilization of presenilin fragmentsStefan 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... - Requirement for small side chain residues within the GxGD-motif of presenilin for gamma-secretase substrate cleavageBlanca 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... - Purification, pharmacological modulation, and biochemical characterization of interactors of endogenous human gamma-secretaseEdith 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... - Expression of the anti-amyloidogenic secretase ADAM10 is suppressed by its 5'-untranslated regionSven 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... - The Nicastrin ectodomain adopts a highly thermostable structureRegina 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... - 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
From the Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University Munich, 80336 Munich, Germany and
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... - Endoplasmic reticulum retention of the gamma-secretase complex component Pen2 by Rer1Christoph 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... - Control of peripheral nerve myelination by the beta-secretase BACE1Michael 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... - Beta-amyloid precursor protein mutants respond to gamma-secretase modulatorsRichard 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.... - Regulated intramembrane proteolysis of the interleukin-1 receptor II by alpha-, beta-, and gamma-secretasePeer 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... - Pathological activity of familial Alzheimer's disease-associated mutant presenilin can be executed by six different gamma-secretase complexesKeiro 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.... - Methylene blue fails to inhibit Tau and polyglutamine protein dependent toxicity in zebrafishFrauke 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... - Parkin phosphorylation and modulation of its E3 ubiquitin ligase activityAyako 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... - Differential effects of Parkinson's disease-associated mutations on stability and folding of DJ-1Karin 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... - Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentationA 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... - Alpha-synuclein has a high affinity for packing defects in a bilayer membrane: a thermodynamics studyBrigitte 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... - Intramembrane proteolysis by gamma-secretaseHarald 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... - Translational repression of the disintegrin and metalloprotease ADAM10 by a stable G-quadruplex secondary structure in its 5'-untranslated regionSven 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... - Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's diseaseMartin 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... - Cellular functions of gamma-secretase-related proteinsChristof 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... - 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-1Harald 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.... - Bepridil and amiodarone simultaneously target the Alzheimer's disease beta- and gamma-secretase via distinct mechanismsStefan 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... - Generation of Abeta38 and Abeta42 is independently and differentially affected by familial Alzheimer disease-associated presenilin mutations and gamma-secretase modulationRichard 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... - A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2bRegina 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... - Requirement of PEN-2 for stabilization of the presenilin N-/C-terminal fragment heterodimer within the gamma-secretase complexStefan 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... - Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathiesManuela 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... - Regional distribution of proteinase K-resistant alpha-synuclein correlates with Lewy body disease stageManuela 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... - Co-expression of nicastrin and presenilin rescues a loss of function mutant of APH-1Dieter 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... - Nicalin and its binding partner Nomo are novel Nodal signaling antagonistsChristof 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... - Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formationDieter 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... - Amyloid precursor protein intracellular domain modulates cellular calcium homeostasis and ATP contentRuna 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... - Proteolytic processing of TAR DNA binding protein-43 by caspases produces C-terminal fragments with disease defining properties independent of progranulinDorothee 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... - Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 productionTobias 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... - Apical sorting of beta-secretase limits amyloid beta-peptide productionAnja 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... - Constitutive phosphorylation of the Parkinson's disease associated alpha-synucleinM 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... - Gamma-secretase activity is associated with a conformational change of nicastrinKeiro 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... - Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkinNicole 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... - Endoproteolysis of the ER stress transducer ATF6 in the presence of functionally inactive presenilinsH 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... - Expression of the Alzheimer protease BACE1 is suppressed via its 5'-untranslated regionSven 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... - Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of NotchM 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... - Separation of presenilin function in amyloid beta-peptide generation and endoproteolysis of NotchL 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... - Mitochondrial dysfunction in Parkinson's diseaseKonstanze 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... - The cell adhesion protein P-selectin glycoprotein ligand-1 is a substrate for the aspartyl protease BACE1Stefan 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... - 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... - Structure/function of alpha-synuclein in health and disease: rational development of animal models for Parkinson's and related diseasesPhilipp J Kahle
Department of Biochemistry, Ludwig Maximilians University, Munich, Germany
J Neurochem 82:449-57. 2002 - Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptideChristian 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... - Single particle detection and characterization of synuclein co-aggregationArmin Giese
Center for Neuropathology and Prion Research, LMU, Munich, Germany
Biochem Biophys Res Commun 333:1202-10. 2005.... - A lipid boundary separates APP and secretases and limits amyloid beta-peptide generationChristoph Kaether
Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Ludwig Maximilans University, , 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... - Initiation and propagation of neurodegenerationChristian 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"?.. - Pore-forming scissors? A first structural glimpse of gamma-secretaseHarald 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... - The biochemical and genetic odyssey to the function of a nicastrin-like proteinChristof 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... - 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... - Physiology and pathophysiology of alpha-synuclein. Cell culture and transgenic animal models based on a Parkinson's disease-associated proteinP 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... - A pathogenic presenilin-1 deletion causes abberrant Abeta 42 production in the absence of congophilic amyloid plaquesH 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... - Phosphorylation of the beta-amyloid precursor protein at the cell surface by ectocasein kinases 1 and 2J 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... - Maturation and pro-peptide cleavage of beta-secretaseA 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... - Phosphorylation regulates intracellular trafficking of beta-secretaseJ 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... - 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... - The cell biology of Alzheimer's disease: uncovering the secrets of secretasesJ Walter
Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
Curr Opin Neurobiol 11:585-90. 2001..Two essential factors for the proteolytic generation of Abeta have been identified, beta-secretase and the presenilins, which might aid the design of drugs against this disease... - Subcellular localization of wild-type and Parkinson's disease-associated mutant alpha -synuclein in human and transgenic mouse brainP 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... - Selective insolubility of alpha-synuclein in human Lewy body diseases is recapitulated in a transgenic mouse modelP 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... - Selective vulnerability of different types of commissural neurons for amyloid beta-protein-induced neurodegeneration in APP23 mice correlates with dendritic tree morphologyEstibaliz Capetillo-Zarate
Department of Neuropathology, University of Bonn, Bonn, Germany
Brain 129:2992-3005. 2006..The vulnerability of different types of neurons to Abeta, thereby, is presumably related to the complexity of their dendritic morphology... - Shedding and gamma-secretase-mediated intramembrane proteolysis of the mucin-type molecule CD43Christian X Andersson
Department of Medical Biochemistry, , Medicinaregatan 9A, 413 90 Gothenburg, Sweden
Biochem J 387:377-84. 2005..From this and the present results, a novel way to explain how mucin-type molecules may transduce intracellular signals can be proposed... - Occurrence and co-localization of amyloid beta-protein and apolipoprotein E in perivascular drainage channels of wild-type and APP-transgenic miceDietmar Rudolf Thal
Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany
Neurobiol Aging 28:1221-30. 2007..In so doing, our results strengthen the hypothesis that an alteration of perivascular drainage supports Abeta-deposition and the development of AD... - Furin-, ADAM 10-, and gamma-secretase-mediated cleavage of a receptor tyrosine phosphatase and regulation of beta-catenin's transcriptional activityLars Anders
Department of Molecular Biology, Max Planck Institute of Biochemistry, Martinsried, Germany
Mol Cell Biol 26:3917-34. 2006..Our results identify intramembrane proteolysis as a regulatory switch in RPTPkappa signaling and implicate PIC in the activation of beta-catenin-mediated transcription... - Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's diseaseMarc Aurel Busche
Institut für Neurowissenschaften, Technische Universität München TUM, 80802 Munchen, Germany
Science 321:1686-9. 2008..Thus, we suggest that a redistribution of synaptic drive between silent and hyperactive neurons, rather than an overall decrease in synaptic activity, provides a mechanism for the disturbed cortical function in Alzheimer's disease... - Presenilin-dependent gamma-secretase on plasma membrane and endosomes is functionally distinctAkio Fukumori
Division of Psychiatry and Behavioral Proteomics, Department of Post Genomics and Diseases, Osaka University Graduate School of Medicine, Osaka, Japan
Biochemistry 45:4907-14. 2006..These results suggest that the precision of cleavage by the PS/gamma-secretase complex may be physiologically regulated by the subcellular location and conditions... - beta-site amyloid precursor protein cleaving enzyme 1 increases amyloid deposition in brain parenchyma but reduces cerebrovascular amyloid angiopathy in aging BACE x APP[V717I] double-transgenic miceMichael Willem
Experimental Genetics Group, LEGT_EGG, K U Leuven, Campus Gasthuisberg O and N 06, B 3000, Leuven, Belgium
Am J Pathol 165:1621-31. 2004..This provides biochemical evidence in vivo for the preferential contribution of N-truncated Abeta to parenchymal amyloid deposition in contrast to vascular amyloid pathology... - Secretion of the Notch-1 Abeta-like peptide during Notch signalingMasayasu Okochi
Department of Post Genomics and Diseases, Division of Psychiatry and Behavioral Proteomics, Osaka University Graduate School of Medicine, Osaka 565 0871, Japan
J Biol Chem 281:7890-8. 2006..We anticipate that this study will open the door to searches for markers of RIP signaling and surrogate markers for Abeta42 production...