Ausgewählte Publikationen:

Becker-Pauly C, Pietrzik CU. 2017: The Metalloprotease Meprin β Is an Alternative β-Secretase of APP. Front Mol Neurosci. Jan 5;9:159.

Wild K, August A, Pietrzik CU, Kins S. 2017: Structure and Synaptic Function of Metal Binding to the Amyloid Precursor Protein and its Proteolytic Fragments. Front Mol Neurosci. Jan 31; 10:21.

Brandscheid C, Schuck F, Reinhardt S, Schäfer KH, Pietrzik CU, Grimm M, Hartmann T, Schwiertz A, Endres K. 2017: Altered Gut Microbiome Composition and Tryptic Activity of the 5xFAD Alzheimer's Mouse Model. J Alzheimers Dis. 56(2):775-788.

Bedau T, Peters F, Prox J, Arnold P, Schmidt F, Finkernagel M, Köllmann S, Wichert R, Otte A, Ohler A, Stirnberg M, Lucius R, Koudelka T, Tholey A, Biasin V, Pietrzik CU, Kwapiszewska G, Becker-Pauly C. 2016: Ectodomain shedding of CD99 within highly conserved regions is mediated by the metalloprotease meprin β and promotes transendothelial cell migration. FASEB J. Dec 21. pii: fj.201601113R.

Becker-Pauly C, Pietrzik CU. 2016: Mice are not Men: ADAM30 Findings Emphasize a Broader Look Towards Murine Alzheimer's Disease Models. EBioMedicine. Jul;9:19-20.

Safina D, Schlitt F, Romeo R, Pflanzner T, Pietrzik CU, Narayanaswami V, Edenhofer F, Faissner A. 2016: Low-density lipoprotein receptor-related protein 1 is a novel modulator of radial glia stem cell proliferation, survival, and differentiation. Glia. Aug;64(8):1363-80.

Schmidt F, Müller M, Prox J, Arnold P, Schönherr C, Tredup C, Minder P, Ebsen H, Janssen O, Annaert W, Pietrzik C, Schmidt-Arras D, Sterchi EE, Becker-Pauly C. 2016: Tetraspanin 8 is an interactor of the metalloprotease meprin β within tetraspanin-enriched microdomains. Biol Chem. Sep 1;397(9):857-69

Schönherr C, Bien J, Isbert S, Wichert R, Prox J, Altmeppen H, Kumar S, Walter J, Lichtenthaler SF, Weggen S, Glatzel M, Becker-Pauly C, Pietrzik CU 2016: Generation of aggregation prone N-terminally truncated amyloid β peptides by meprin β depends on the sequence specificity at the cleavage site. Molecular Neurodegeneration. Feb 19;11(1):19.

Afrimzon E, Zurgil N, Sobolev M, Shafran Y, Langer K, Zlatev I, Wronski R, Windisch M, von Briesen H, Schmidt R, Pietrzik CU, Deutsch M 2016: Detection and analysis of human serum albumin nanoparticles within phagocytic cells at the resolution of individual live cell or single 3D multicellular spheroid. Journal of Nanoparticle Research. 17(12),492

Storck SE, Meister S, Nahrath J, Meißner JN, Schubert N, Di Spiezio A, Baches S, Vandenbroucke RE, Bouter Y, Prikulis I, Korth C, Weggen S, Heimann A, Schwaninger M, Bayer TA, Pietrzik CU. 2016: Endothelial LRP1 transports amyloid-β1-42 across the blood-brain barrier. J Clin Invest. Jan 4;126(1):123-36.

Rabiej VK, Pflanzner T, Wagner T, Götze K, Storck S, Eble JA, Weggen S, Mueller-Klieser W, Pietrzik CU. 2015: Low density lipoprotein receptor-related protein 1 mediated endocytosis of β1-integrin influences cell adhesion and cell migration. Exp Cell Res. Jan 1;340(1):102-15.

Jäckle F, Schmidt F, Wichert R, Arnold P, Prox J, Mangold M, Ohler A, Pietrzik CU, Koudelka T, Tholey A, Gütschow M, Stirnberg M, Becker-Pauly C. 2015: Metalloprotease meprin β is activated by transmembrane serine protease matriptase-2 at the cell surface thereby enhancing APP shedding. Biochem J. 5 Aug 15;470(1):91-103.

Arnold P, Schmidt F, Prox J, Zunke F, Pietrzik C, Lucius R, Becker-Pauly C. 2015: Calcium negatively regulates meprin β activity and attenuates substrate cleavage. FASEB J. Aug;29(8):3549-57. doi: 10.1096/fj.15-272310. Epub 2015 May 8.

Meister S, Storck SE, Hameister E, Behl C, Weggen S, Clement AM, Pietrzik CU. 2015: Expression of the ALS-causing variant hSOD1(G93A) leads to an impaired integrity and altered regulation of claudin-5 expression in an in vitro blood-spinal cord barrier model. J Cereb Blood Flow Metab. Jul;35(7):1112-21.

Tucher J, Linke D, Koudelka T, Cassidy L, Tredup C, Wichert R, Pietrzik C, Becker-Pauly C, Tholey A. 2014:
LC-MS based cleavage site profiling of the proteases ADAM10 and ADAM17 using proteome-derived peptide libraries.
J Proteome Res. 2014 Apr 4;13(4):2205-14.

Martínez Vera NP, Schmidt R, Langer K, Zlatev I, Wronski R, Auer E, Havas D, Windisch M, von Briesen H, Wagner S, Stab J, Deutsch M, Pietrzik C, Fazekas F, Ropele S.2014: Tracking of magnetite labeled nanoparticles in the rat brain using MRI.
PLoS One. 2014 Mar 14;9(3):e92068.

Meister S, Zlatev I, Stab J, Docter D, Baches S, Stauber RH, Deutsch M, Schmidt R, Ropele S, Windisch M, Langer K, Wagner S, von Briesen H, Weggen S, Pietrzik CU. 2013: Nanoparticulate flurbiprofen reduces amyloid-β42 generation in an in vitro blood-brain barrier model.
Alzheimers Res Ther. 2013 Nov 27;5(6):51.

Maier W, Bednorz M, Meister S, Roebroek A, Weggen S, Schmitt U, Pietrzik CU. 2013: LRP1 is critical for the surface distribution and internalization of the NR2B NMDA receptor subtype.
Mol Neurodegener. 2013 Jul 17;8:25.

Wagner T, Dieckmann M, Jaeger S, Weggen S, Pietrzik CU. 2013: Stx5 is a novel interactor of VLDL-R to affect its intracellular trafficking and processing.
Exp Cell Res. 2013 Aug 1;319(13):1956-72. doi: 10.1016/j.yexcr.2013.05.010. Epub 2013 May 20.

Gil SY, Youn BS, Byun K, Huang H, Namkoong C, Jang PG, Lee JY, Jo YH, Kang GM, Kim HK, Shin MS, Pietrzik CU, Lee B, Kim YB, Kim MS. 2013: Clusterin and LRP2 are critical components of the hypothalamic feeding regulatory pathway.
Nat Commun. 2013;4:1862. doi: 10.1038/ncomms2896

Rennhack A, Jumpertz T, Ness J, Baches , Pietrzik CU, Weggen S, Bulic B. 2012: Synthesis of a potent photoreactive acidic γ-secretase modulator for target identification in cells.
Bioorg Med Chem. 2012 Nov 1;20(21):6523-32.

Jefferson T, Auf dem Keller U, Bellac C, Metz VV, Broder C, Hedrich J, Ohler A, Maier W, Magdolen V, Sterchi E, Bond JS, Jayakumar A, Traupe H, Chalaris A, Rose-John S, Pietrzik CU, Postina R, Overall CM, Becker-Pauly C. 2012: The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin β and ADAM10.
Cell Mol Life Sci. 2012 Sep 1. [Epub ahead of print]

Bien J, Jefferson T, Causevic M, Jumpertz T, Muenter L, Multhaup G, Weggen S, Becker-Pauly C, Pietrzik CU. 2012: The metalloprotease meprin β generates amino terminal truncated Aβ-peptide species.
J Biol Chem. 2012 Aug 9. [Epub ahead of print]

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 γ-Secretase Modulators with a Novel Activity Profile by Text-Based Virtual Screening.
ACS Chem Biol. 2012 Jul 2. [Epub ahead of print]

Wagner S, Zensi A, Wien SL, Tschickardt SE, Maier W, Vogel T, Worek F, Pietrzik CU, Kreuter J, von Briesen H. 2012: Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model. PLoS One. 2012;7(3):e32568. Epub 2012 Mar 1.

Müller UC, Pietrzik CU, Deller T. 2012: The physiological functions of the β-amyloid precursor protein APP.
Exp Brain Res. 2012 Apr;217(3-4):325-9. No abstract available.

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-β transcytosis across the blood-brain barrier. J Cereb Blood Flow Metab. 2012 Apr;32(4):628-32. doi: 10.1038/jcbfm.2012.7. Epub 2012 Feb 1

Jumpertz T, Rennhack A, Ness J, Baches S, Pietrzik CU, Bulic B, Weggen S. 2012: Presenilin Is the Molecular Target of Acidic γ-Secretase Modulators in Living Cells. PLoS One. 2012;7(1):e30484. Epub 2012 Jan 6.

Isbert S, Wagner K, Eggert S, Schweitzer A, Multhaup G, Weggen S, Kins S, Pietrzik CU. 2011: APP dimer formation is initiated in the endoplasmic reticulum and differs between APP isoforms. Cell Mol Life Sci. 2011 Nov 22. [Epub ahead of print]

Wagner T, Pietrzik CU. 2011: The role of lipoprotein receptors on the physiological function of APP. Exp Brain Res. 2011 Sep 23. [Epub ahead of print]

Jefferson T, Causevic M, Auf dem Keller U, Schilling O, Isbert S, Geyer R, Maier W, Tschickardt S, Jumpertz T, Weggen S, Bond JS, Overall CM, Pietrzik CU, Becker-Pauly C. 2011: Metalloprotease Meprin β Generates Nontoxic N-terminal Amyloid Precursor Protein Fragments in vivo. J Biol Chem. 2011 Aug 5;286(31):27741-50. Epub 2011 Jun 6.

Heneka MT, Kummer MP, Weggen S, Bulic B, Multhaup G, Münter L, Hüll M, Pflanzner T, Pietrzik CU. 2011: Molecular Mechanisms and Therapeutic Application of NSAIDs and Derived Compounds in Alzheimer's Disease. Curr Alzheimer Res. 2011 Mar;8(2):115-31. Review.

Rolyan H, Feike AC, Upadhaya AR, Waha A, Van Dooren T, Haass C, Birkenmeier G, Pietrzik CU, Van Leuven F, Thal DR. 2011: Amyloid-β protein modulates the perivascular clearance of neuronal apolipoprotein E in mouse models of Alzheimer's disease.  J Neural Transm. 2011 Jan 6. [Epub ahead of print]

Hahn S, Brüning T, Ness J, Czirr E, Baches S, Gijsen H, Korth C, Pietrzik CU, Bulic B, Weggen S. 2010: Presenilin-1 (PSEN1) but not amyloid precursor protein (APP) mutations present in mouse models of Alzheimer's disease attenuate the response of cultured cells to γ-secretase modulators (GSMs) regardless of their potency and structure. J Neurochem. 2010 Nov 20. doi: 10.1111/j.1471-4159.2010.07118.x. [Epub ahead of print]PMID: 21091478 [PubMed - as supplied by publisher]Related citations

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. Curr Alzheimer Res. 2010 Aug 2. [Epub ahead of print]PMID: 20704558 [PubMed - as supplied by publisher]Related citations

Pflanzner T, Janko MC, André-Dohmen B, Reuss S, Weggen S, Roebroek AJ, Kuhlmann CR, Pietrzik CU. 2010: LRP1 mediates bidirectional transcytosis of amyloid-beta across the blood-brain barrier. Neurobiol Aging. 2010 Jul 12. [Epub ahead of print]PMID: 20630619 [PubMed - as supplied by publisher]Related citations

Kirschbaum KM, Uhr M, Holthoewer D, Namendorf C, Pietrzik C, Hiemke C, Schmitt U. 2010: Pharmacokinetics of acute and sub-chronic aripiprazole in P-glycoprotein deficient mice. Neuropharmacology. 2010 Nov;59(6):474-9. Epub 2010 Jul 3.PMID: 20599439 [PubMed - in process]Related citations

Reekmans SM, Pflanzner T, Gordts PL, Isbert S, Zimmermann P, Annaert W, Weggen S, Roebroek AJ, Pietrzik CU. 2009: Inactivation of the proximal NPXY motif impairs early steps in LRP1 biosynthesis. Cell Mol Life Sci. 2009 Oct 25. [Epub ahead of print]PMID: 19856143 [PubMed - as supplied by publisher]

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: Related articles alpha-secretase mediated conversion of the amyloid precursor protein derived membrane stub C99 to C83 limits Abeta generation. J Neurochem. 2009 Oct 5. [Epub ahead of print]PMID: 19804379 [PubMed - as supplied by publisher]Related articles

Kuhlmann CR, Librizzi L, Closhen D, Pflanzner T, Lessmann V, Pietrzik CU, de Curtis M, Luhmann HJ. 2008: Mechanisms of C-reactive protein-induced blood-brain barrier disruption. Stroke. 2009 Apr;40(4):1458-66. Epub 2009 Feb 26.

Tamboli IY, Prager K, Thal DR, Thelen KM, Dewachter I, Pietrzik CU, St George-Hyslop P, Sisodia SS, De Strooper 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. 2008 Nov 12;28(46):12097-106.

Jaeger S and Pietrzik C.U. 2008: Functional role of lipoprotein receptors in Alzheimer's disease. Curr Alzheimer Res. Feb;5(1):15-25.

Martin A, Jaeger S, Kuhlmann C, Roebroek A, Luhmann H, Laatsch A, Weggen S, Lessmann V, Pietrzik C. U. 2008: The functional role of LRP1 in tissue plasminogen activator mediated activation of the NMDA receptor. J. Biol. Chem. May 2;283(18):12004-13.

Leuchtenberger S, Maler J, Czirr E, Ness J, Lichtenthaler SF, Esselmann H, Pietrzik C.U., Wiltfang J, Weggen S. 2008: Nonsteroidal Anti-Inflammatory Drugs and Ectodomain Shedding of the Amyloid Precursor Protein. Neurodegener Dis. Mar 18.

Czirr E, Cottrell BA, Leuchtenberger S, Kukar T, Ladd TB, Esselmann H, Paul S, Schubenel R, Torpey JW, Pietrzik C.U., Golde TE, Wiltfang J, Baumann K, Koo EH, Weggen S. 2008: Independent generation of Abeta42 and Abeta38 peptide species by gamma-secretase. J. Biol. Chem. Jun 20;283(25):17049-54. Epub 2008 Apr 21.

Waldron E, Isbert S, Kern A, Jaeger S, Martin AM, Hébert SS, Behl C, Weggen S, De Strooper B, Pietrzik C.U. 2008: Increased AICD generation does not result in increased nuclear translocation or activation of target gene transcription. Exp Cell Res. Aug 1;314(13):2419-33. Epub 2008 May 17.

Waldron E, Heilig C, Schweitzer A, Nadella N, Jaeger S, Martin AM, Weggen S, Brix K, Pietrzik C.U. 2008: LRP1 modulates APP trafficking along early compartments of the secretory pathway. Neurobiol. Dis. Aug;31(2):188-97. Epub 2008 May 3.

Utter S, Tamboli IY, Walter J, Upadhaya AR, Birkenmeier G, Pietrzik C.U., Ghebremedhin E, Thal DR. 2008: Cerebral Small Vessel Disease induced Apolipoprotein E leakage is associated with Alzheimer Disease and the accumulation of Amyloid ß-Protein in Perivascular Astrocytes. J. Neuropathol. Exp. Neurol. Sep;67(9):842-856.

Ring S, Weyer SW, Kilian SB, Waldron E, Pietrzik CU, Filippov MA, Herms J, Buchholz C, Eckman CB, Korte M, Wolfer DP, Muller UC. 2007: The secreted beta-amyloid precursor protein ectodomain APPs alpha is sufficient to rescue the anatomical, behavioral, and electrophysiological abnormalities of APP-deficient mice. J Neurosci. 2007 Jul 18;27(29):7817-26.

Czirr E, Leuchtenberger S, Dorner-Ciossek C, Schneider A, Jucker M, Koo EH, Pietrzik CU, Baumann K, Weggen S. 2007: Insensitivity to Abeta42-lowering nonsteroidal anti-inflammatory drugs and gamma-secretase inhibitors is common among aggressive presenilin-1 mutations. J Biol Chem. 2007 Aug 24;282(34):24504-13.

Waldron E, Jaeger S, Pietrzik C.U. 2006: Functional role of the low-density lipoprotein receptor-related protein in Alzheimer's disease. Neurodegener Dis. 2006;3(4-5):233-8.

Neumann S, Schöbel S, Jäger S, Haass C, Pietrzik C.U., Lichtenthaler SF 2005: APLP1 influences endocytosis and proteolytic processing of the amyloid precursor protein. J. Biol. Chem. 2006 Mar 17;281(11):7583-94.

Leuchtenberger S, Kummer MP, Kukar T, Czirr E, Sagi SA, Berdeaux R, Pietrzik C.U., Golde T, Koo EH, Weggen S 2006: Inhibitors of the Rho-effector Rho-kinase (ROCK) modulate amyloid-ß (Aß) secretion but lack selectivity for Aß42. J. Neurochem. 2006 Jan;96(2):355-65.

Pietrzik C, Behl C. 2005: Concepts for the treatment of Alzheimer's disease: molecular mechanisms and clinical application.Int J Exp Pathol. 86(3):173-85.

Lleo A, Waldron E, von Arnim CA, Herl L, Tangredi MM, Peltan ID, Strickland DK, Koo EH, Hyman BT, Pietrzik CU, Berezovska O. 2005: Low density lipoprotein receptor-related protein (LRP) interacts with presenilin 1 and is a competitive substrate of the amyloid precursor protein (APP) for gamma-secretase. J Biol Chem. 22;280(29):27303-9. (*authors contributed equally to this work).<//font>

Yoon IS, Pietrzik CU, Kang DE, Koo EH. 2005:Sequences from the low density lipoprotein receptor-related protein (LRP) cytoplasmic domain enhance amyloid beta protein production via the beta-secretase pathway without altering amyloid precursor protein/LRP nuclear signaling. J Biol Chem. 2005 May 20;280(20):20140-7. Epub 2005 Mar 16.

Goodenough S., Schleusner D., Pietrzik C.U. and Behl C. 2005: Glycogen Synthase kinase 3ß links neuroprotection by 17ß-estradiol to key Alzheimer processes. Neuroscience 132(3):581-9.

Pietrzik C.U., Yoon I.-S., Jaeger S., Busse T., Weggen S., Koo E.H. . 2004: FE65 Constitutes the Functional Link between the Low-Density Lipoprotein Receptor-Related Protein and the Amyloid Precursor Protein. J. Neuroscience April 28, 2004-24(17):4259-4265

Weggen S, Eriksen JL, Sagi SA, Pietrzik C.U., Ozols V, Fauq A, Golde TE, Koo EH. 2003: Evidence that nonsteroidal anti-inflammatory drugs decrease Abeta 42 production by direct modulation of gamma-secretase activity. J. Biol. Chem. 278(34):31831-7.

Weggen S, Eriksen JL, Sagi SA, Pietrzik CU, Golde TE, Koo EH. 2003: A beta42-lowering nonsteroidal anti-inflammatory drugs preserve intramembrane cleavage of the amyloid precursor protein and ErbB-4 receptor and signaling through the APP intracellular domain. J. Biol. Chem. 278(34):31831-7.

Pietrzik C.U., Busse T., Merriam D.E., Weggen S. and Edward H. Koo. 2002: The cytoplasmic domain of the LDL receptor-related protein regulates multiple steps in amyloid precursor protein processing. EMBO J. 21(21):5691-700.

Leem J.Y., Saura C.A., Pietrzik C., Christianson J., Wanamaker C., King L.T., Veselits M.L., Tomita T., Gasparini L., Iwatsubo T., Xu H., Green W.N., Koo, E.H. and G. Thinakaran. 2002: A role for presenilin 1 in regulating the delivery of amyloid precursor protein to the cell surface. Neurobiol. Disease Oct;11(1):64-82.

Weggen S., Eriksen J.L., Das P., Sagi S.A., Wang R., Pietrzik C.U., Findlay K.A., Smith T.E., Murphy M.P., Bulter T., Kang D.E., Marquez-Sterling N., Golde T.E. and E.H. Koo. 2001: A subset of NSAIDs lower amyloidogenic Ab42 independent of COX activity. Nature, 414:212-216.

Soriano S., Lu D., Chandra S., Pietrzik C.U. and E.H. Koo 2001: The amyloidogenic pathway of amyloid precursor protein (APP) is independent of its cleavage by caspases. J. Biol. Chem. 276(31): 29045-50.

Kang D.E.*, Pietrzik C.U.*, Baum L., Chevallier N., Merriam D.E., Kounnas M.Z., Wagner S.L., Troncoso J.C., Kawas C.H., Katzman R. and E.H. Koo . 2000: Modulation of amyloid b-protein clearance and Alzheimer's disease susceptibility by the LDL receptor-related protein pathway. J. Clin. Invest. 106(9):1159-1166. (*authors contributed equally to this work).

Hoffmann J., Pietrzik C.U., Kummer M.P., Twiesselmann C., Bauer C. and V. Herzog 1999: Binding and selective detection of the secretory N-terminal domain of the Alzheimer Amyloid Precursor Protein on cell surfaces. J. Histochem. Cytochem. 47(3):373-82.

Pietrzik C.U., Hoffmann J., Stöber K., Chen C.-Y., Bauer C., Otero D.A.C., Roch J-M and V. Herzog 1998: From Differentiation to Proliferation: The Secretory Amyloid Precursor Protein as a local Mediator of Growth in Thyroid Epithelial Cells. Proc. Natl. Acad. Sci. USA 17;95(4):1770-5.

Overdick M., Czermak A., Fischer P., Herzog V., Kjensmo T., Ljunggren K., Nygard E., Pietrzik C., Schwan T., Strand S.-E., Straver J., Weilhammer P., Wermes N. and K. Yoshioka 1997: A “Bioscope” system using double-sided silicon strip detectors and self-triggering read-out chips. Nucl. Instr. Meth. A 392: 173-177.

Popp G.M., Graebert K.S., Pietrzik C.U., Rosentreter S.M., Lemansky P. and V.Herzog 1996: Growth Regulation of Rat Thyrocytes (FRTL-5 Cells) by the Secreted Ectodomain of the ß-Amyloid Precursor-Like Proteins. Endocrinology 137: 5122-5125.




Metalloprotease Meprin {beta} Generates Nontoxic N-terminal Amyloid Precursor Protein Fragments in Vivo.


Synthesis of a potent photoreactive acidic γ-secretase modulator for target identification in cells. 

Bioorg Med Chem. 2012 Nov 1;20(21):6523-32.