Verbund Amyloid

Publikationen

Publikationen 2. Förderphase des KNDD (seit 2011)

Die nachfolgende Liste zeigt ausschließlich Publikationen, die durch Mittel des KNDD direkt unterstützt wurden. KNDD Wissenschaftler - Laborleiter sowie Doktoranden und Postdoktoranden - sind fett unterlegt.

  • Pester O, Barret P, Hornburg D, Hornburg P, Pröbstle R, Widmaier S, Kutzner C, Dürrbaum M, Kapurniotu A, Sanders CR, Scharnagl C, Langosch D (2013) The backbone dynamics of the amyloid precursor protein transmembrane helix provides a rationale for the sequential cleavage mechanism of gamma-secretase. J Am Chem Soc 135:1317-1329
  • Tesseur I, Pimenova AA, Lo AC, Ciesielska M, Lichtenthaler SF, De Maeyer JH, Schuurkes JA, D'Hooge R, De Strooper B (2013) Chronic 5-HT4 receptor activation decreases Abeta production and deposition in hAPP/PS1 mice. Neurobiol Aging 34:1779-1789
  • Hofmann JP, Denner P, Nussbaum-Krammer C, Kuhn PH, Suhre MH, Scheibel T, Lichtenthaler SF, Schätzl HM, Bano D, Vorberg IM (2013) Cell-to-cell propagation of infectious cytosolic protein aggregates. Proc Natl Acad Sci U S A 110:5951-5956
  • Hogl S, van Bebber F, Dislich B, Kuhn PH, Haass C, Schmid B, Lichtenthaler SF (2013) Label-free quantitative analysis of the membrane proteome of Bace1 protease knock-out zebrafish brains. Proteomics 13:1519-1527
  • Schmid B, Hruscha A, Hogl S, Banzhaf-Strathmann J, Strecker K, van der Zee J, Teucke M, Eimer S, Hegermann J, Kittelmann M, Kremmer E, Cruts M, Solchenberger B, Hasenkamp L, van Bebber F, van Broeckhoven C, Edbauer C, Lichtenthaler SF, Haass C (2013) Loss of ALS-associated TDP-43 in zebrafish causes muscle degeneration, vascular dysfunction, and reduced motor neuron axon outgrowth. Proc Natl Acad Sci USA 110:4986-4991
  • Walker LC, Jucker M (2013) The seeds of dementia. Scientific American 308: 53-57
  • Kretner B, Fukumori A, Kuhn PH, Perez-Revuelta BI, Lichtenthaler SF, Haass C, Steiner H (2013) Important functional role of residue x of the presenilin GxGD protease active site motif for APP substrate cleavage specificity and substrate selectivity of amma-secretase. J Neurochem 125:144-156
  • Voss M, Fukumori A, Kuhn PH, Künzel U, Klier B, Grammer G, Haug-Kröper M, Kremmer E, Lichtenthaler S, Steiner H, Schröder B, Haass C, Fluhrer R (2013) Foamy virus envelope protein is a substrate for signal peptide peptidase like-3 (SPPL3). J Biol Chem 287:43401-43409
  • Cochet M, Donneger R, Cassier E, Gaven F, Lichtenthaler SF, Marin P, Bockaert J, Dumuis A, Claeysen S (2013) 5-HT4 Receptors constitutively promote the non-amyloidogenic pathway of APP cleavage and interact with ADAM10. ACS Chemical Neuroscience 4:130-140
  • Bien J, Jefferson T, Causević M, Jumpertz T, Munter L, Multhaup G, Weggen S, Becker-Pauly C, Pietrzik CU (2012) The metalloprotease meprin beta generates amino terminal-truncated amyloid beta peptide species. J Biol Chem 287:33304-13
  • Wirths O, Dins A, Bayer TA (2012) APP accumulation and/or intraneuronal Abeta accumulation? The 3xTg-AD mouse model revisited. Journal of Alzheimers Disease 28: 897-904
  • Page RM, Münch A, Horn T, Kuhn PH, Colombo A, Reiner O, Boutros M, Steiner H, Lichtenthaler SF, Haass C (2012) Loss of PAFA1B2 reduces Abeta generation by promoting the degradation of APP C-terminal fragments. J Neurosci 32:18204-18214
  • Augustin R, Endres K, Reinhardt S, Kuhn PH, Lichtenthaler SF, Hansen J, Wurst W, Trümbach D (2012). Computational identification and experimental validation of microRNAs binding to the Alzheimer related gene ADAM10. BMC Med Genet 13:35
  • Lichtenthaler SF (2012). Alpha-Secretase Cleavage of the Amyloid Precursor Protein: Proteolysis Regulated by Signaling Pathways and Protein Trafficking. Curr Alzheimer Res 9:165-177.
  • Varvel NH, Grathwohl SA, Baumann F, Liebig C, Bosch A, Brawek B, Thal DR, Charo IF, Heppner FL, Aguzzi A, Garaschuk O, Ransohoff RM, Jucker M. (2012) Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells. Proc Natl Acad Sci USA 109:18150-5
  • Weggen S, Beher D (2012) Molecular consequences of amyloid precursor protein and presenilin mutations causing autosomal-dominant Alzheimer’s disease. Alzheimers Res Ther March 30; 4:9
  • Zettl H, Ness J, Hähnke V, Beher D, Jumpertz T, Saric A, Baumann K, Pietrzik CU, Bulic B, Schneider G, Weggen S (2012) Discovery of gamma-secretase modulators with a novel activity profile by text-based virtual screening. ACS Chemical Biology 7:1488-95
  • Rennhack A, Jumpertz T, Ness J, Baches S, Pietrzik CU, Weggen S, Bulic B (2012) Synthesis of a potent photoreactive acidic gamma-secretase modulator for target identification in cells. Bioorg Med Chem 20:6523-32
  • Kuhn PH, Koroniak K, Hogl S, Colombo A, Zeitschel U, Willem M, Volbracht C, Schepers U, Imhof A, Hoffmeister A, Haass C, Roßner S, Bräse S, Lichtenthaler SF (2012) Secretome protein enrichment identifies physiological BACE1 protease substrates in neurons. EMBO J 31:3157-68
  • Colombo A, Wang H, Kuhn PH, Page R, Kremmer E, Dempsey PJ, Crawford HC, Lichtenthaler SF (2012). Constitutive alpha- and beta-secretase cleavages of the amyloid precursor protein are partially coupled in neurons, but not in frequently used cell lines. Neurobiol Dis 49C:137-147
  • Dislich B, Lichtenthaler SF (2012) The membrane-bound aspartyl protease BACE1: molecular and functional properties in Alzheimer's disease and beyond. Front Physiol 3:8
  • Wirths O, Bayer TA (2012) Intraneuronal Abeta accumulation and neurodegeneration: lessons from transgenic models. Life Sci 91:1148-115
  • Pflanzner T, Petsch B, André-Dohmen B, Müller-Schiffmann A, Tschickardt S, Weggen S, Stitz L, Korth C, Pietrzik CU (2012) Cellular prion protein participates in amyloid-beta transcytosis across the blood-brain barrier. Journal of Cerebral Blood Flow and Metabolism 32:628-32
  • Winkler E, Kamp F, Scheuring J, Ebke A, Fukumori A, Steiner H (2012) Generation of Alzheimer disease-associated Aeta42/43 by amma-secretase can directly be inhibited by modulation of membrane thickness, J Biol Chem 287:21326-34
  • Jumpertz T, Rennhack A, Ness J, Baches S, Pietrzik CU, Bulic B, Weggen S (2012) Presenilin is the molecular target of acidic gamma-secretase modulators in living cells. PLoS one 7:e30484
  • Hillmann A, Hahn S, Schilling S, Hoffmann T, Demuth HU, Bulic B, Schneider-Axmann T, Bayer TA, Weggen S, and Wirths O (2012) No improvement after chronic ibuprofen treatment in the 5XFAD mouse model of Alzheimer's disease. Neurobiol. Aging 33: 833.e839–50
  • Hamaguchi T, Eisele YS, Varvel NH, Lamb BT, Walker LC, Jucker M (2012) The presence of Abeta seeds and not age per se is critical to the initiation of Abeta deposition in the brain. Acta Neuropathol 123:31-7
  • Rosen RF, Fritz JJ, Dooyema J, Cintron AF, Hamaguchi T, Lah JJ, Levine H 3rd, Jucker M, Walker LC (2012) Exogenous seeding of cerebral beta-amyloid deposition in beta-APP-transgenic rats. J Neurochem 120:660-6
  • Jawhar S, Trawicka A, Jenneckens C, Bayer TA, Wirths O (2012) Motor deficits, neuron loss and reduced anxiety coinciding with axonal degeneration and intraneuronal Abeta aggregation in the 5XFAD mouse model of Alzheimer’s disease. Neurobiol Aging 33:196.e29-40
  • Dislich B, Than ME, Lichtenthaler SF (2011) Specific amino acids in the BAR domain allow homodimerization and prevent heterodimerization of sorting nexin 33. Biochem J 433:75-83
  • Moss ML, Powell G, Miller MA, Edwards L, Qi B, Sang QX, De Strooper B, Tesseur I, Lichtenthaler SF, Taverna M, Zhong JL, Dingwall C, Ferdous T, Schlomann U, Zhou P, Griffith LG, Lauffenburger DA, Petrovich R, Bartsch JW (2011) ADAM9 inhibition increases membrane activity of ADAM10 and controls alpha-secretase processing of amyloid precursor protein. J Biol Chem 286:40443-40451
  • Hogl S, Kuhn PH, Colombo A, Lichtenthaler SF (2011) Determination of the proteolytic cleavage sites of the amyloid precursor-like protein 2 by the proteases ADAM10, BACE1 and gamma-secretase. PLoS ONE 6:e21337
  • Augustin R, Lichtenthaler SF, Greeff M, Hansen J, Wurst W, Trümbach D (2011) Bioinformatics identification of modules of transcription factor binding sites in Alzheimer's disease-related genes by in silico promoter analysis and microarrays. Int J Alzheimers Dis 2011:154325
  • Lichtenthaler SF (2011) Alpha-secretase in Alzheimer's disease: molecular identity, regulation and therapeutic potential. J Neurochem 116:10-21
  • Lichtenthaler SF, Haass C, Steiner H (2011) Regulated intramembrane proteolysis - lessons from amyloid precursor protein processing. J Neurochem 117(5):779-796
  • Bulic B, Ness J, Hahn S, Rennhack A, Jumpertz T, Weggen S (2011) Chemical biology, molecular mechanism and clinical perspective of gamma-secretase modulators in Alzheimer’s disease. Current Neuropharmacology 9:598-622
  • Hieke M, Ness J, Steri R, Greiner C, Werz O, Schubert-Zsilavecz M, Weggen S, Zettl H (2011) SAR studies of acidic dual gamma-secretase/PPARgamma modulators. Bioorganic and Medicinal Chemistry 19:5372-82
  • Kretner B, Fukumori A, Gutsmiedl A, Page RM, Luebbers T, Galley G, Baumann K, Haass C, Steiner H (2011) Attenuated Aeta42 responses to low potency amma-secretase modulators can be overcome for many pathogenic presenilin mutants by second-generation compounds. J Biol Chem 286:15240-15251  
  • Ebke A, Luebbers T, Fukumori A, Shirotani K, Haass C, Baumann K, Steiner H (2011) Novel gamma-secretase enzyme modulators directly target presenilin protein. J Biol Chem 286:37181-37186  
  • Jawhar, S., Wirths, O., and Bayer, T. A. (2011) Pyroglutamate Abeta - a hatchet man in Alzheimer disease. J Biol Chem 286, 38825–38832
  • Langer F, Eisele YS, Fritschi SK, Staufenbiel M, Walker LC, Jucker M (2011) Soluble Abeta seeds are potent inducers of cerebral beta-amyloid deposition. J Neurosci 31: 14488-95
  • Jucker M, Walker LC (2011) Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders. Ann Neurol 70:532-40
  • Hahn S, Brüning T, Ness J, Czirr E, Baches S, Gijsen H, Korth CU, Bulic B, Weggen S (2011). Presenilin-1 but not amyloid precursor protein mutations present in mouse models of Alzheimer's disease attenuate the response of cultured cells to gamma-secretase modulators regardless of their potency and structure. J Neurochem 116:385-95
  • Pflanzner T, Janko MC, André-Dohmen B, Reuss S, Weggen S, Roebroek AJM, Kuhlmann CRW, Pietrzik CU (2011) LRP1 mediates bidirectional transcytosis of amyloid-beta across the blood-brain-barrier. Neurobiology of Aging 32:2323.e1-11

Publikationen 1. Förderphase des KNDD (2008-2010)

  • Lammich S, Buell D, Zilow S, Ludwig A-K, Nuscher B, Lichtenthaler SF, Prinzen C, Fahrenholz F, and Haass C (2010) Expression of the anti-amyloidogenic alpha-secretase ADAM10 is suppressed by its 5’-untranslated region. J Biol Chem 285: 15753-60 
  • Mitterreiter S, Page RM, Kamp F, Hopson J, Winkler E, Ha HR, Hamid R, Herms J, Mayer TU, Nelson DJ, Steiner H, Stahl T, Zeitschel U, Roßner S, Haass C, Lichtenthaler SF (2010) Bepridil and amiodarone simultaneously target the Alzheimer’s disease beta- and gamma-secretase via distinct mechanisms. J Neurosci 30: 8974-83
  • Kuhn PH, Wang H, Dislich B, Zeitschel U, Ellwart JW, Kremmer E, Roßner S, Lichtenthaler SF (2010) ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary beurons, EMBO J 29: 3020-32
  • Ullrich S, Münch A, Neumann S, Kremmer E, Tatzelt J, Lichtenthaler SF (2010) The novel membrane protein TMEM59 modulates complex glycosylation, cell surface expression and secretion of the amyloid precursor protein, J Biol Chem 285: 20664-74
  • Höttecke N, Liebeck M, Baumann K, Schubenel R, Winkler E, Steiner H, Schmidt B (2010) Inhibition of gamma-secretase by the CK1 inhibitor IC261 does not depend on CK1delta. Bioorg Med Chem Lett 20: 2958-63
  • Page RM, Gutsmiedl A, Fukumori A, Winkler E, Haass C, Steiner H (2010) APP mutants respond to gamma-secretase modulators. J Biol Chem 285: 17798-810 
  • Richter L, Munter LM, Ness J, Hildebrand PW, Dasari M, Unterreitmeier S, Bulic B, Beyermann M, Gust R, Reif B, Weggen S, Langosch D, Multhaup G (2010) Abeta42-lowering compounds directly bind to Abeta and interfere with APP transmembrane dimerization. Proc Natl Acad Sci 107: 14597-602
  • Hieke M, Ness J, Steri R, Dittrich M, Greiner C, Werz O, Baumann K, Schubert-Zsilavecz M, Weggen S, Zettl H (2010) Design, synthesis and biological evaluation of a novel class of gamma-secretase modulators with PPARgamma activity. J Med Chem 53: 4691-700
  • Zettl H, Weggen S, Schneider P, Schneider G (2010) Exploring the chemical space of gamma-secretase modulators. Trends Pharmacol Sci 31 402-10
  • Reekmans SM, Pflanzner T, Gordts PL, Isbert S, Zimmermann P, Annaert W, Weggen S, Roebroek AJ, Pietrzik CU (2010) Inactivation of the proximal NPXY motif impairs early steps in LRP1 biosynthesis. Cell Mol Life Sci 67: 135-45
  • Pflanzner T, Kuhlmann CR, Pietrzik CU (2010) Blood brain barrier models for the investigation of transporter- and receptor mediated amyloid beta clearance in Alzheimer’s disease. Current Alzheimer Disease 7: 578-90
  • Fluhrer R, Steiner H, Haass C (2009) Intramembrane proteolysis by signal peptide peptidases: a comparative discussion of GXGD-type aspartyl proteases. J Biol Chem 284: 13975-9
  • Kuhlmann CR, Librizzi L, Closhen D, Pflanzner T, Lessmann V, Pietrzik CU, de Curtis M, Luhmann HJ (2009) Mechanisms of C-reactive protein-induced blood-brain barrier disruption. Stroke 40:1458-66.
  • Jäger S, Leuchtenberger S, Martin A, Czirr E, Wesselowski J, Dieckmann M, Waldron E, Korth C, Koo EH, Heneka M, Weggen S, Pietrzik CU (2009) Alpha-secretase mediated conversion of the amyloid precursor protein derived membrane stub C99 to C83 limits Abeta generation. J Neurochem 111:1369-82.
  • Grathwohl SA, Kälin RE, Bolmont T, Prokop S, Winkelmann G, Kaeser SA, Odenthal J, Radde R, Eldh T, Gandy S, Aguzzi A, Staufenbiel M, Mathews PM, Wolburg H, Heppner FL, Jucker M (2009) Formation and maintenance of Alzheimer's disease beta-amyloid plaques in the absence of microglia. Nat Neurosci 12: 1361-3
  • Aslund A, Sigurdson CJ, Klingstedt T, Grathwohl S, Bolmont T, Dickstein DL, Glimsdal E, Prokop S, Lindgren M, Konradsson P, Holtzman DM, Hof PR, Heppner FL, Gandy S, Jucker M, Aguzzi A, Hammarström P, Nilsson KP (2009) Novel pentameric thiophene derivatives for in vitro and in vivo optical imaging of a plethora of protein aggregates in cerebral amyloidoses. ACS Chem Biol 4: 673-84
  • Eisele YS, Bolmont T, Heikenwalder M, Langer F, Jacobson LH, Yan ZX, Roth K, Aguzzi A, Staufenbiel M, Walker LC, Jucker M (2009) Induction of cerebral beta-amyloidosis: intracerebral versus systemic Abeta inoculation. Proc Natl Acad Sci U S A 106 12926-31
  • Eisele YS, Obermüller U, Heilbronner G, Baumann F, Kaeser SA, Wolburg H, Walker LC, Staufenbiel M, Jucker M (2009) Peripherally applied Abeta-containing inoculates induce cerebral beta-amyloidosis. Science. 330: 980-82
  • Page RM, Baumann K, Tomioka M, Perez-Revuelta BI, Fukumori A, Jacobsen H, Flohr A, Luebbers T, Ozmen L, Steiner H, Haass C (2008) Generation of Abeta38 and Abeta42 is independently and differentially affected by familial Alzheimer disease-associated presenilin mutations and gamma-secretase modulation. J Biol Chem 283: 677-83
  • Steiner H, Fluhrer R, Haass C (2008) Intramembrane proteolysis by γ-secretase. J Biol Chem 283: 29627-31 
  • Tamboli IY, Prager K, Thal DR, Thelen KR, Dewachter I, Pietrzik CU, St. George-Hyslop P, Sisodia SS, DeStrooper B, Heneka MT, Filippov MA, Müller U, van Leuven F, Lütjohann D, Walter J (2008) Loss of gamma-secretase function impairs endocytosis of lipoprotein particles and membrane cholesterol homeostasis. J Neurosci 28: 12097-106
  • Bolmont T, Haiss F, Eicke D, Radde R, Mathis CA, Klunk WE, Kohsaka S, Jucker M, Calhoun ME. (2008) Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance. J Neurosci 28: 4283-92