Selected Publications

Full list of publications in PubMed

Bradshaw NJ, Trossbach SV, Köber S, Walter S, Prikulis I, Weggen S, Korth C. Disrupted in Schizophrenia 1 regulates the processing of reelin in the perinatal cortex. Schizophr Res. 2017 Apr 19. pii: S0920-9964(17)30200-1. doi: 10.1016/j.schres.2017.04.012. [Epub ahead of print] PubMed

Walter S, Jumpertz T, Hüttenrauch M, Ogorek I, Gerber H, Storck SE, Zampar S, Dimitrov M, Lehmann S, Lepka K, Berndt C, Wiltfang J, Becker-Pauly C, Beher D, Pietrzik CU, Fraering PC, Wirths O, Weggen S. The metalloprotease ADAMTS4 generates N-truncated Aβ4-x species and marks oligodendrocytes as a source of amyloidogenic peptides in Alzheimer's disease. Acta Neuropathol. 2019 Feb;137(2):239-257. doi: 10.1007/s00401-018-1929-5. Epub 2018 Nov 13. PubMed

Hüttenrauch M, Ogorek I, Klafki H, Otto M, Stadelmann C, Weggen S, Wiltfang J, Wirths O. Glycoprotein NMB: a novel Alzheimer's disease associated marker expressed in a subset of activated microglia. Acta Neuropathol Commun. 2018 Oct 19;6(1):108. doi: 10.1186/s40478-018-0612-3. PubMed

Storck SE, Hartz AMS, Bernard J, Wolf A, Kachlmeier A, Mahringer A, Weggen S, Pahnke J, Pietrzik CU. The concerted amyloid-beta clearance of LRP1 and ABCB1/P-gp across the blood-brain barrier is linked by PICALM. Brain Behav Immun. 2018 Oct;73:21-33. doi: 10.1016/j.bbi.2018.07.017. Epub 2018 Jul 21. PubMed

Goel P1, Jumpertz T2, Tichá A3, Ogorek I2, Mikles DC3, Hubalek M, Pietrzik CU, Strisovsky K, Schmidt B, Weggen S. Discovery and validation of 2-styryl substituted benzoxazin-4-ones as a novel scaffold for rhomboid protease inhibitors. Bioorg Med Chem Lett. 2018 May 1;28(8):1417-1422. doi: 10.1016/j.bmcl.2018.02.017. Epub 2018 Feb 9. PubMed

Lesuis SL, Weggen S, Baches S, Lucassen PJ, Krugers HJ. Targeting glucocorticoid receptors prevents the effects of early life stress on amyloid pathology and cognitive performance in APP/PS1 mice. Transl Psychiatry. 2018 Mar 1;8(1):53. doi: 10.1038/s41398-018-0101-2. PubMed

Goel P, Jumpertz T, Mikles DC, Tichá A, Nguyen MTN, Verhelst S, Hubalek M, Johnson DC, Bachovchin DA, Ogorek I, Pietrzik CU, Strisovsky K, Schmidt B, Weggen S. Discovery and Biological Evaluation of Potent and Selective N-Methylene Saccharin-Derived Inhibitors for Rhomboid Intramembrane Proteases. Biochemistry. 2017 Dec 26;56(51):6713-6725. doi: 10.1021/acs.biochem.7b01066. Epub 2017 Dec 12. PubMed

Wirths O, Walter S, Kraus I, Klafki HW, Stazi M, Oberstein TJ, Ghiso J, Wiltfang J, Bayer TA, Weggen S. N-truncated Aβ4-x peptides in sporadic Alzheimer's disease cases and transgenic Alzheimer mouse models. Alzheimers Res Ther. 2017 Oct 4;9(1):80. doi: 10.1186/s13195-017-0309-z. PubMed

Hüttenrauch M, Walter S, Kaufmann M, Weggen S, Wirths O. Limited Effects of Prolonged Environmental Enrichment on the Pathology of 5XFAD Mice. Mol Neurobiol. 2017 Oct;54(8):6542-6555. doi: 10.1007/s12035-016-0167-x. Epub 2016 Oct 12. PubMed

Schönherr C, Bien J1, Isbert S, Wichert R, Prox J, Altmeppen H, Kumar S, Walter J, Lichtenthaler SF, Weggen S, Glatzel M, Becker-Pauly C, Pietrzik CU. Generation of aggregation prone N-terminally truncated amyloid ß peptides by meprin ß depends on the sequence specificity at the cleavage site. Mol Neurodegener. 2016 Feb 19;11(1):19. doi: 10.1186/s13024-016-0084-5. PubMed

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. Endothelial LRP1 transports amyloid-ß1-42 across the blood-brain barrier. J Clin Invest. 2016 Jan 4;126(1):123-36. doi: 10.1172/JCI81108. Epub 2015 Nov 30. PubMed

Rabiej VK, Pflanzner T, Wagner T, Goetze K, Storck SE, Eble JA, Weggen S, Mueller-Klieser W, Pietrzik CU. Low density lipoprotein receptor-related protein 1 mediated endocytosis of ß1-integrin influences cell adhesion and cell migration. Exp Cell Res. 2016 Jan 1;340(1):102-15. doi: 10.1016/j.yexcr.2015.11.020. Epub 2015 Nov 22. PubMed

 Antonios G, Borgers H, Richard BC, Brauß A, Meißner J, Weggen S, Pena V, Pillot T, Davies SL, Bakrania P, Matthews D, Brownlees J, Bouter Y, Bayer TA. Alzheimer therapy with an antibody against N-terminal Abeta 4-X and pyroglutamate Abeta 3-X. Sci Rep. 2015 Dec 2;5:17338. doi: 10.1038/srep17338. PubMed

Meister S, Storck SE, Hameister E, Behl C, Weggen S, Clement AM, Pietrzik CU. Expression of the ALS-causing variant hSOD1G93A 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. 2015 Jul;35(7):1112-21. doi: 10.1038/jcbfm.2015.57. Epub 2015 Apr 8. PubMed

Flesch D, Ness J, Lamers C, Dehm F, Popella S, Steri R, Ogorek I, Hieke M, Dannhardt G, Werz O, Weggen S, Schubert-Zsilavecz M. SAR-studies of gamma-secretase modulators with PPARgamma-agonistic and 5-lipoxygenase-inhibitory activity for Alzheimer's disease. Bioorg Med Chem Lett. 2015 Feb 15;25(4):841-6. doi: 10.1016/j.bmcl.2014.12.073. Epub 2014 Dec 30. PubMed

Richard BC, Kurdakova A, Baches S, Bayer TA, Weggen S, Wirths O. Gene Dosage Dependent Aggravation of the Neurological Phenotype in the 5XFAD Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2015 Jan 1;45(4):1223-36. doi: 10.3233/JAD-143120. PubMed

Hüttenrauch M, Baches S, Gerth J, Bayer TA, Weggen S, Wirths O. Neprilysin Deficiency Alters the Neuropathological and Behavioral Phenotype in the 5XFAD Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2015 Jan 1;44(4):1291-302. doi: 10.3233/JAD-142463. PubMed

Gowert NS, Donner L, Chatterjee M, Eisele YS, Towhid ST, Münzer P, Walker B, Ogorek I, Borst O, Grandoch M, Schaller M, Fischer JW, Gawaz M, Weggen S, Lang F, Jucker M, Elvers M. Blood platelets in the progression of Alzheimer's disease. PLoS One. 2014 Feb 28;9(2):e90523. doi: 10.1371/journal.pone.0090523. eCollection 2014. PubMed

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. Nanoparticulate flurbiprofen reduces amyloid-ß42 generation in an in vitro blood-brain barrier model. Alzheimers Res Ther. 2013 Nov 27;5(6):51. doi: 10.1186/alzrt225. eCollection 2013. PubMed

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. Aug 1;319(13):1956-72. doi: 10.1016/j.yexcr.2013.05.010. PubMed

Naumann EC, Göring S, Ogorek I, Weggen S, Schmidt B. (2013) Membrane anchoring gamma-secretase modulators with terpene-derived moieties. Bioorg Med Chem Lett. Jul 1;23(13):3852-6. doi: 10.1016/j.bmcl.2013.04.070.  PubMed

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. Jul 17;8:25. doi: 10.1186/1750-1326-8-25, PubMed

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. PubMed

Bien J, Jefferson T, Causevic M, Jumpertz T, Muenter L, Multhaup G, Weggen S, Becker-Pauly C, Pietrzik CU (2012) The metalloprotease meprin beta generates amino terminal truncated Abeta-peptide species. Journal of Biological Chemistry; 287:33304-13. PubMed

Hartenfeller M, Zettl H, Walter M, Rupp M, Reisen F, Proschak E, Weggen S, Stark H, Schneider G (2012) DOGS: Reaction-driven de novo design of bioactive compounds. PLoS Computational Biology; 8:e1002380. PubMed

Pflanzner T, Petsch B, Andre-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. PubMed

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. PubMed

Isbert S, Wagner K, Schweitzer A, Kins S, Multhaup G, Weggen S, Pietrzik CU (2012) APP dimer formation is initiated in the endoplasmic reticulum and differs between APP isoforms. Cellular and Molecular Life Sciences; 69:1353-75 PubMed

Hillmann A, Hahn S, Schilling S, Hoffmann, T, Demuth HU, Bulic B, Schneider-Axmann T, Bayer TA, Weggen S, Wirths O (2012) No improvement after chronic ibuprofen treatment in the 5XFAD mouse model of Alzheimer’s disease. Neurobiology of Aging; 33:833.e39-50. PubMed

Sagi SA, Lessard CB, Winden KD, Maruyama H, Koo JC, Weggen S, Kukar TL, Golde TE, Koo EH (2011) Substrate sequence influences gamma-secretase modulator activity: role of the transmembrane domain of the amyloid precursor protein. Journal of Biological Chemistry; 286:39794-803. PubMed

Jefferson T, Causevic M, auf dem Keller U, Schilling O, Isbert S, Geyer R, Maier W, Tschickardt S, Postina, R, Metz VV, Jumpertz T, Weggen S, Bond JS, Overall CM, Pietrzik CU, Becker-Pauly C (2011) The metalloprotease meprin beta generates non-toxic N-terminal amyloid precursor protein fragments in vivo. Journal of Biological Chemistry; 286:27741-50. PubMed

Hahn S, Brüning T, Ness J, Czirr E, Baches S, Gijsen H, Korth C, Pietrzik C, 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. Journal of Neurochemistry; 116:385-95. PubMed

Pflanzner T, Janko MC, Andre-Dohmen B, Reus S, Weggen S, Roebroek AJM, Kuhlmann CR, Pietrzik CU (2011) LRP1 mediates bidirectional transcytosis of amyloid-beta across the blood-brain barrier. Neurobiology of Aging; 32:2323.e1-11. PubMed

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. Journal of Medicinal Chemistry; 53:4691-700. PubMed

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) Amyloid beta 42 peptide (Abeta42)-lowering compounds directly bind to Abeta and interfere with amyloid precursor protein (APP) transmembrane dimerization. Proceedings of the National Academy of Sciences of the United States of America; 107:14597-602. PubMed

Reekmans SM, Pflanzner T, Gordts P, Isbert S, Zimmermann P, Annaert W, Weggen S, Roebroek AJM, Pietrzik CU (2010) Inactivation of the proximal NPXY motif impairs early steps in LRP1 biosynthesis. Cellular and Molecular Life Sciences; 67:135-45. PubMed

Kummer MP, Maruyama H, Huelsmann C, Baches S, Weggen S, Koo EH (2009) Formation of PMEL 17 amyloid is regulated by juxtamembrane metalloproteinase cleavage and the resulting C-terminal fragment is a substrate for gamma-secretase. Journal of Biological Chemistry; 284: 2296-306. PubMed

Czirr E, Cottrell BA, Leuchtenberger S, Kukar T, Ladd TV, Esselmann H, Paul S, Schubenel R, Torpey JW, Pietrzik CU, Golde TE, Wiltfang J, Baumann KH, Koo EH, Weggen S (2008) Independent generation of Abeta42 and Abeta38 peptide species by gamma-secretase. Journal of Biological Chemistry; 283:17049-54. PubMed

Leuchtenberger S, Maler J, Czirr E, Ness J, Lichtenthaler S, Pietrzik C, Wiltfang J, and Weggen S. (2008) Non-steroidal anti-inflammatory drugs (NSAIDs) and ectodomain shedding of the amyloid precursor protein (APP). Neurodegenerative Diseases; Epub March 18. PubMed

Martin AM, Kuhlmann C, Trossbach S, Jaeger S, Waldron E, Roebroek A, Luhmann HJ, Laatsch A, Weggen S, Lessmann V, Pietrzik CU (2008) The functional role of the second NPXY motif of the LRP beta-chain in tPA-mediated activation of NMDA receptors. Journal of Biological Chemistry; 283:12004-13. PubMed

Czirr E, Leuchtenberger S, Dorner-Ciossek C, Schneider A, Jucker M, Koo EH, Pietrzik CU, Baumann KH, and Weggen S (2007) Insensitivity to Abeta42-lowering non-steroidal anti-inflammatory drugs (NSAIDs) and gamma-secretase inhibitors is common among aggressive presenilin-1 (PS1) mutations. Journal of Biological Chemistry; 282:24504-13. PubMed

Kukar T, Murphy MP, Eriksen JL, Sagi SA, Weggen S, Smith TE, Ladd T, Khan MA, Beard J, Dodson M, Merit S, Ozols VV, Anastasiadis PZ, Das P, Fauq A, Koo EH, Golde TE (2005) Diverse compounds mimic Alzheimer’s disease causing mutations by augmenting Abeta42 production. Nature Medicine; 11:545-50. PubMed

Pietrzik CU, Yoon IS, Jaeger S, Busse T, Weggen S, Koo EH (2004) FE65 constitutes the func­tional link between the low-density lipoprotein receptor-related protein and the amyloid precursor protein. Journal of Neuroscience; 24:4259-65. PubMed

Weggen S, Eriksen J, Sagi S, Pietrzik CU Golde TE, Koo EH (2003) Abeta42-lowering nonsteroidal anti-inflammatory drugs preserve intramembrane cleavage in the amyloid precursor protein and ErbB-4 and signaling through the APP intracellular domain. Journal of Biological Chemistry; 278:30748-54. PubMed

Weggen S, Eriksen J, Sagi SA, Pietrzik CU, Ozols V, Fauq A, Golde TE, Koo EH (2003) Evidence that nonsteroidal anti-inflammatory drugs decrease Abeta42 production by direct modulation gamma-secretase activity. Journal of Biological Chemistry; 278:31831-7. PubMed

Sagi SA, Weggen S, Eriksen J, Golde TE, Koo EH (2003) The non-cyclooxygenase targets of non-steroidal anti-inflammatory drugs, lipoxygenases, peroxisome proliferator-activated receptor, inhibitor of kappa B kinase, and NF kappa B, do not reduce amyloid beta 42 production.. Journal of Biological Chemistry; 278:31825-30. PubMed

Eriksen J, Sagi S, Monnier TE, Weggen S, McClendon DC, Ozols V, Jessing KW, Zavitz KH, Koo EH, Golde TE (2003) NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. Journal of Clinical Investigation; 112:440-9. PubMed

Pietrzik CU, Busse T, Merriam DE, Weggen S, Koo EH (2002) The cytoplasmic domain of the LDL receptor-related protein regulates multiple steps in amyloid precursor protein processing. EMBO Journal; 21:5691-5700. PubMed

Weggen S, Eriksen JL, Das P, Sagi SA, Wang R, Pietrzik CU, Findlay KA, Smith TE, Murphy MP, Bulter T, Kang DE, Marquez-Sterling N, Golde TE, and Koo EH (2001) A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature; 414:212-6.PubMed

Review Articles

 

Weggen S, Beher D (2012) Molecular consequences of amyloid precursor protein and presenilin mutations causing autosomal-dominant Alzheimer’s disease. Alzheimer Research & Therapy; March 30;4:9. PubMed

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. PubMed

Zettl H, Weggen S, Schneider P, Schneider G (2010) Exploring the chemical space of gamma-secretase modulators. Trends in Pharmacological Sciences; 31:402-10. PubMed

Weggen S, Rogers M, and Eriksen JL (2007) NSAIDs: small molecules for prevention of Alzheimer’s disease or precursors for future drug development? Trends In Pharmacological Sciences, 28:536-43. PubMed

Czirr E and Weggen S (2006) Gamma-secretase modulation with Abeta42-lowering non-steroidal anti-inflammatory drugs and derived compounds. Neurodegenerative Diseases; 3:298-304. PubMed

Leuchtenberger S, Beher D, and Weggen S (2006) Selective modulation of Abeta42 production in Alzheimer‘s disease: non-steroidal anti-inflammatory drugs and beyond. Current Pharmaceutical Design; 12:4337-55. PubMed

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