ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
Recently Viewed
You have not visited any articles yet, Please visit some articles to see contents here.
CONTENT TYPES

Figure 1Loading Img
RETURN TO ISSUEAccelerated Publicat...Accelerated PublicationNEXT

On the Seeding and Oligomerization of pGlu-Amyloid Peptides (in vitro)

View Author Information
Probiodrug AG, and ACGT ProGenomics AG, Weinbergweg 22, 06120 Halle/Saale, Germany
Cite this: Biochemistry 2006, 45, 41, 12393–12399
Publication Date (Web):September 20, 2006
https://doi.org/10.1021/bi0612667
Copyright © 2006 American Chemical Society
Article Views
1434
Altmetric
-
Citations
LEARN ABOUT THESE METRICS
Read OnlinePDF (111 KB)

Abstract

Abstract Image

Oligomerization of amyloid β (Aβ) peptides is the decisive event in the development of Alzheimer's disease (AD), the most common neurogenerative disorder in developed countries. Recent evidence links this conformation-driven process to primary- and secondary-structure modifications of Aβ. The N and C terminus of deposited Aβ has been shown to possess conspicuous heterogeneity. While the C-terminally longer form of Aβ, i.e., Aβ (42), is considered more amyloidogenic, the role of the N-terminal modifications, e.g., truncation and glutamate cyclization accounting for the majority of the deposited peptides, is less understood. In the present study, we characterized the oligomerization and seeding capacity of pGlu-amyloid peptides using two unrelated techniques based on flow cytometry or flourescence dye binding. Under different conditions and irrespective of the C terminus of Aβ, i.e., Aβ40 or 42, pGlu-modified peptides displayed an up to 250-fold accelerated initial formation of aggregates compared to unmodified Aβ. The accelerated seed formation is accompanied by a change in the oligomerization kinetics because of N-terminal pGlu formation. Furthermore, the formation of mixed aggregates consisting of either pGlu-Aβ (3−42) or ADan or ABri and Aβ (1−42) was investigated by Aβ fluorescence labeling in flow cytometry. The results suggest that pGlu-modified peptides are potential seeding species of aggregate formation in vivo. The data presented here and the abundance of pGlu peptides in amyloidoses, such as FBD and AD, suggest pGlu-amyloid peptides as a species with biophysical characteristics that might be in particular crucial for the initiation of the disease.

 Probiodrug AG.

§

 ACGT ProGenomics AG.

*

 To whom correspondence should be addressed:  Probiodrug AG, Weinbergweg 22, 06120 Halle, Germany. Telephone:  +49-345-5559900. Fax:  +49-345-5559901. E-mail:  [email protected] probiodrug.de.

Cited By

This article is cited by 189 publications.

  1. Soumya Mukherjee, Keyla A. Perez, Celine Dubois, Rebecca M. Nisbet, Qiao-Xin Li, Shiji Varghese, Liang Jin, Ian Birchall, Victor A. Streltsov, Laura J. Vella, Catriona McLean, Kevin J. Barham, Blaine R. Roberts, Colin L. Masters. Citrullination of Amyloid-β Peptides in Alzheimer’s Disease. ACS Chemical Neuroscience 2021, 12 (19) , 3719-3732. https://doi.org/10.1021/acschemneuro.1c00474
  2. Chenshu Xu, Yi-nan Wang, Haiqiang Wu. Glutaminyl Cyclase, Diseases, and Development of Glutaminyl Cyclase Inhibitors. Journal of Medicinal Chemistry 2021, 64 (10) , 6549-6565. https://doi.org/10.1021/acs.jmedchem.1c00325
  3. Zhi-Wen Hu, Dan Fai Au, Letticia Cruceta, Liliya Vugmeyster, Wei Qiang. N-Terminal Modified Aβ Variants Enable Modulations to the Structures and Cytotoxicity Levels of Wild-Type Aβ Fibrils through Cross-Seeding. ACS Chemical Neuroscience 2020, 11 (14) , 2058-2065. https://doi.org/10.1021/acschemneuro.0c00316
  4. Ewelina Stefaniak, Wojciech Bal. CuII Binding Properties of N-Truncated Aβ Peptides: In Search of Biological Function. Inorganic Chemistry 2019, 58 (20) , 13561-13577. https://doi.org/10.1021/acs.inorgchem.9b01399
  5. Van-Hai Hoang, Van T. H. Ngo, Minghua Cui, Nguyen Van Manh, Phuong-Thao Tran, Jihyae Ann, Hee-Jin Ha, Hee Kim, Kwanghyun Choi, Young-Ho Kim, Hyerim Chang, Stephani Joy Y. Macalino, Jiyoun Lee, Sun Choi, Jeewoo Lee. Discovery of Conformationally Restricted Human Glutaminyl Cyclase Inhibitors as Potent Anti-Alzheimer’s Agents by Structure-Based Design. Journal of Medicinal Chemistry 2019, 62 (17) , 8011-8027. https://doi.org/10.1021/acs.jmedchem.9b00751
  6. Jason O. Matos, Greg Goldblatt, Jaekyun Jeon, Bo Chen, and Suren A. Tatulian . Pyroglutamylated Amyloid-β Peptide Reverses Cross β-Sheets by a Prion-Like Mechanism. The Journal of Physical Chemistry B 2014, 118 (21) , 5637-5643. https://doi.org/10.1021/jp412743s
  7. Daniel Ramsbeck, Mirko Buchholz, Birgit Koch, Livia Böhme, Torsten Hoffmann, Hans-Ulrich Demuth, and Ulrich Heiser . Structure–Activity Relationships of Benzimidazole-Based Glutaminyl Cyclase Inhibitors Featuring a Heteroaryl Scaffold. Journal of Medicinal Chemistry 2013, 56 (17) , 6613-6625. https://doi.org/10.1021/jm4001709
  8. Bruno Alies, Christian Bijani, Stéphanie Sayen, Emmanuel Guillon, Peter Faller, and Christelle Hureau . Copper Coordination to Native N-Terminally Modified versus Full-Length Amyloid-β: Second-Sphere Effects Determine the Species Present at Physiological pH. Inorganic Chemistry 2012, 51 (23) , 12988-13000. https://doi.org/10.1021/ic302097d
  9. I. W. Hamley . The Amyloid Beta Peptide: A Chemist’s Perspective. Role in Alzheimer’s and Fibrillization. Chemical Reviews 2012, 112 (10) , 5147-5192. https://doi.org/10.1021/cr3000994
  10. Birgit Koch, Petr Kolenko, Mirko Buchholz, David Ruiz Carrillo, Christoph Parthier, Michael Wermann, Jens-Ulrich Rahfeld, Gunter Reuter, Stephan Schilling, Milton T. Stubbs, and Hans-Ulrich Demuth . Crystal Structures of Glutaminyl Cyclases (QCs) from Drosophila melanogaster Reveal Active Site Conservation between Insect and Mammalian QCs. Biochemistry 2012, 51 (37) , 7383-7392. https://doi.org/10.1021/bi300687g
  11. Gözde Eskici and Paul H. Axelsen . Copper and Oxidative Stress in the Pathogenesis of Alzheimer’s Disease. Biochemistry 2012, 51 (32) , 6289-6311. https://doi.org/10.1021/bi3006169
  12. Huiyuan Li, Zhenming Du, Dahabada H. J. Lopes, Erica A. Fradinger, Chunyu Wang, and Gal Bitan . C-Terminal Tetrapeptides Inhibit Aβ42-Induced Neurotoxicity Primarily through Specific Interaction at the N-Terminus of Aβ42. Journal of Medicinal Chemistry 2011, 54 (24) , 8451-8460. https://doi.org/10.1021/jm200982p
  13. Eric Martineau, Janna M. de Guzman, Lioudmila Rodionova, Xianqi Kong, Paul M. Mayer, Ahmed M. Aman. Investigation of the noncovalent interactions between anti-amyloid agents and amyloid β peptides by ESI-MS. Journal of the American Society for Mass Spectrometry 2010, 21 (9) , 1506-1514. https://doi.org/10.1016/j.jasms.2010.05.007
  14. Mirko Buchholz, Antje Hamann, Susanne Aust, Wolfgang Brandt, Livia Böhme, Torsten Hoffmann, Stephan Schilling, Hans-Ulrich Demuth and Ulrich Heiser . Inhibitors for Human Glutaminyl Cyclase by Structure Based Design and Bioisosteric Replacement. Journal of Medicinal Chemistry 2009, 52 (22) , 7069-7080. https://doi.org/10.1021/jm900969p
  15. Dagmar Schlenzig, Susanne Manhart, Yeliz Cinar, Martin Kleinschmidt, Gerd Hause, Dieter Willbold, Susanne Aileen Funke, Stephan Schilling and Hans-Ulrich Demuth . Pyroglutamate Formation Influences Solubility and Amyloidogenicity of Amyloid Peptides. Biochemistry 2009, 48 (29) , 7072-7078. https://doi.org/10.1021/bi900818a
  16. Simon C. Drew, Colin L. Masters and Kevin J. Barnham . Alanine-2 Carbonyl is an Oxygen Ligand in Cu2+ Coordination of Alzheimer’s Disease Amyloid-β Peptide − Relevance to N-Terminally Truncated Forms. Journal of the American Chemical Society 2009, 131 (25) , 8760-8761. https://doi.org/10.1021/ja903669a
  17. Anna Gardberg, Lezlee Dice, Kathleen Pridgen, Jan Ko, Paul Patterson, Susan Ou, Ronald Wetzel and Chris Dealwis . Structures of Aβ-Related Peptide−Monoclonal Antibody Complexes,. Biochemistry 2009, 48 (23) , 5210-5217. https://doi.org/10.1021/bi9001216
  18. Holger Cynis, Eike Scheel, Takaomi C. Saido, Stephan Schilling and Hans-Ulrich Demuth . Amyloidogenic Processing of Amyloid Precursor Protein: Evidence of a Pivotal Role of Glutaminyl Cyclase in Generation of Pyroglutamate-Modified Amyloid-β. Biochemistry 2008, 47 (28) , 7405-7413. https://doi.org/10.1021/bi800250p
  19. Magdalena Z. Wiloch, Martin Jönsson-Niedziółka. Very small changes in the peptide sequence alter the redox properties of Aβ(11–16)-Cu(II) and pAβ(11–16)-Cu(II) β-amyloid complexes. Journal of Electroanalytical Chemistry 2022, 922 , 116746. https://doi.org/10.1016/j.jelechem.2022.116746
  20. Magdalena Z. Wiloch, Natalia Baran, Martin Jönsson‐Niedziółka. The Influence of Coordination Mode on the Redox Properties of Copper Complexes with Aβ(3‐16) and Its Pyroglutamate Counterpart pAβ(3‐16). ChemElectroChem 2022, 9 (17) https://doi.org/10.1002/celc.202200623
  21. Naoto Watamura, Kaori Sato, Takaomi C. Saido. Mouse models of Alzheimer's disease for preclinical research. Neurochemistry International 2022, 158 , 105361. https://doi.org/10.1016/j.neuint.2022.105361
  22. Yidan Zhang, Yifan Wang, Zhan Zhao, Weixun Peng, Peng Wang, Ximing Xu, Chenyang Zhao. Glutaminyl cyclases, the potential targets of cancer and neurodegenerative diseases. European Journal of Pharmacology 2022, 931 , 175178. https://doi.org/10.1016/j.ejphar.2022.175178
  23. Gregory Hook, Thomas Reinheckel, Junjun Ni, Zhou Wu, Mark Kindy, Christoph Peters, Vivian Hook, . Cathepsin B Gene Knockout Improves Behavioral Deficits and Reduces Pathology in Models of Neurologic Disorders. Pharmacological Reviews 2022, 74 (3) , 600-629. https://doi.org/10.1124/pharmrev.121.000527
  24. Eric E Abrahamson, Julia K Kofler, Carl R Becker, Julie C Price, Kathy L Newell, Bernardino Ghetti, Jill R Murrell, Catriona A McLean, Oscar L Lopez, Chester A Mathis, William E Klunk, Victor L Villemagne, Milos D Ikonomovic. 11C-PiB PET can underestimate brain amyloid-β burden when cotton wool plaques are numerous. Brain 2022, 145 (6) , 2161-2176. https://doi.org/10.1093/brain/awab434
  25. Hermann Russ, Michele Mazzanti, Chris Parsons, Katrin Riemann, Alexander Gebauer, Gerhard Rammes. The Small Molecule GAL-201 Efficiently Detoxifies Soluble Amyloid β Oligomers: New Approach towards Oral Disease-Modifying Treatment of Alzheimer’s Disease. International Journal of Molecular Sciences 2022, 23 (10) , 5794. https://doi.org/10.3390/ijms23105794
  26. Deborah O. T. Alawode, Nick C. Fox, Henrik Zetterberg, Amanda J. Heslegrave. Alzheimer’s Disease Biomarkers Revisited From the Amyloid Cascade Hypothesis Standpoint. Frontiers in Neuroscience 2022, 16 https://doi.org/10.3389/fnins.2022.837390
  27. Ricardo Apátiga-Pérez, Luis O. Soto-Rojas, B. Berenice Campa-Córdoba, Nabil Itzi Luna-Viramontes, Elvis Cuevas, Ignacio Villanueva-Fierro, Miguel Angel Ontiveros-Torres, Marely Bravo-Muñoz, Paola Flores-Rodríguez, Linda Garcés-Ramirez, Fidel de la Cruz, José Francisco Montiel-Sosa, Mar Pacheco-Herrero, José Luna-Muñoz. Neurovascular dysfunction and vascular amyloid accumulation as early events in Alzheimer's disease. Metabolic Brain Disease 2022, 37 (1) , 39-50. https://doi.org/10.1007/s11011-021-00814-4
  28. E. G. B. Vijverberg, T. M. Axelsen, A. R. Bihlet, K. Henriksen, F. Weber, K. Fuchs, J. E. Harrison, K. Kühn-Wache, P. Alexandersen, N. D. Prins, Philip Scheltens. Rationale and study design of a randomized, placebo-controlled, double-blind phase 2b trial to evaluate efficacy, safety, and tolerability of an oral glutaminyl cyclase inhibitor varoglutamstat (PQ912) in study participants with MCI and mild AD—VIVIAD. Alzheimer's Research & Therapy 2021, 13 (1) https://doi.org/10.1186/s13195-021-00882-9
  29. Nguyen Van Manh, Van-Hai Hoang, Van T.H. Ngo, Jihyae Ann, Tae-ho Jang, Jung-Hye Ha, Jae Young Song, Hee-Jin Ha, Hee Kim, Young-Ho Kim, Jiyoun Lee, Jeewoo Lee. Discovery of highly potent human glutaminyl cyclase (QC) inhibitors as anti-Alzheimer's agents by the combination of pharmacophore-based and structure-based design. European Journal of Medicinal Chemistry 2021, 226 , 113819. https://doi.org/10.1016/j.ejmech.2021.113819
  30. Carolin Hofmann, Annika Sander, Xing Xing Wang, Martina Buerge, Bettina Jungwirth, Laura Borgstedt, Matthias Kreuzer, Claudia Kopp, Kenji Schorpp, Kamyar Hadian, Carsten T. Wotjak, Tim Ebert, Maarten Ruitenberg, Christopher G. Parsons, Gerhard Rammes, . Inhalational Anesthetics Do Not Deteriorate Amyloid-β-Derived Pathophysiology in Alzheimer’s Disease: Investigations on the Molecular, Neuronal, and Behavioral Level. Journal of Alzheimer's Disease 2021, 84 (3) , 1193-1218. https://doi.org/10.3233/JAD-201185
  31. Violetta N. Pivtoraiko, Tamara Racic, Eric E. Abrahamson, Victor L. Villemagne, Benjamin L. Handen, Ira T. Lott, Elizabeth Head, Milos D. Ikonomovic. Postmortem Neocortical 3H-PiB Binding and Levels of Unmodified and Pyroglutamate Aβ in Down Syndrome and Sporadic Alzheimer’s Disease. Frontiers in Aging Neuroscience 2021, 13 https://doi.org/10.3389/fnagi.2021.728739
  32. Deborah O T Alawode, Amanda J Heslegrave, Nick C Fox, Henrik Zetterberg. Donanemab removes Alzheimer's plaques: what is special about its target?. The Lancet Healthy Longevity 2021, 2 (7) , e395-e396. https://doi.org/10.1016/S2666-7568(21)00144-6
  33. Faisal Abedin, Suren A. Tatulian. Mutual structural effects of unmodified and pyroglutamylated amyloid β peptides during aggregation. Journal of Peptide Science 2021, 27 (6) https://doi.org/10.1002/psc.3312
  34. P. Ghosh, J. Pateras, V. Rangachari, A. Vaidya. A network thermodynamic analysis of amyloid aggregation along competing pathways. Applied Mathematics and Computation 2021, 393 , 125778. https://doi.org/10.1016/j.amc.2020.125778
  35. Thore Hettmann, Stephen D. Gillies, Martin Kleinschmidt, Anke Piechotta, Koki Makioka, Cynthia A. Lemere, Stephan Schilling, Jens-Ulrich Rahfeld, Inge Lues. Development of the clinical candidate PBD-C06, a humanized pGlu3-Aβ-specific antibody against Alzheimer’s disease with reduced complement activation. Scientific Reports 2020, 10 (1) https://doi.org/10.1038/s41598-020-60319-5
  36. Helen Crehan, Bin Liu, Martin Kleinschmidt, Jens-Ulrich Rahfeld, Kevin X. Le, Barbara J. Caldarone, Jeffrey L. Frost, Thore Hettmann, Birgit Hutter-Paier, Brian O’Nuallain, Mi-Ae Park, Marcelo F. DiCarli, Inge Lues, Stephan Schilling, Cynthia A. Lemere. Effector function of anti-pyroglutamate-3 Aβ antibodies affects cognitive benefit, glial activation and amyloid clearance in Alzheimer’s-like mice. Alzheimer's Research & Therapy 2020, 12 (1) https://doi.org/10.1186/s13195-019-0579-8
  37. Oliver Wirths, Silvia Zampar. Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models. International Journal of Molecular Sciences 2020, 21 (21) , 8144. https://doi.org/10.3390/ijms21218144
  38. Vivian Hook, Michael Yoon, Charles Mosier, Gen Ito, Sonia Podvin, Brian P. Head, Robert Rissman, Anthony J. O'Donoghue, Gregory Hook. Cathepsin B in neurodegeneration of Alzheimer's disease, traumatic brain injury, and related brain disorders. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 2020, 1868 (8) , 140428. https://doi.org/10.1016/j.bbapap.2020.140428
  39. Tomoki Nakayoshi, Koichi Kato, Eiji Kurimoto, Akifumi Oda. Computational studies on nonenzymatic pyroglutamylation mechanism of N-terminal glutamic acid residues in aqueous conditions*. Molecular Physics 2020, 118 (14) , e1702727. https://doi.org/10.1080/00268976.2019.1702727
  40. Joerg Neddens, Magdalena Daurer, Stefanie Flunkert, Kerstin Beutl, Tina Loeffler, Lauren Walker, Johannes Attems, Birgit Hutter-Paier, . Correlation of pyroglutamate amyloid β and ptau Ser202/Thr205 levels in Alzheimer’s disease and related murine models. PLOS ONE 2020, 15 (7) , e0235543. https://doi.org/10.1371/journal.pone.0235543
  41. Larissa-Nele Schaffert, Wayne G. Carter. Do Post-Translational Modifications Influence Protein Aggregation in Neurodegenerative Diseases: A Systematic Review. Brain Sciences 2020, 10 (4) , 232. https://doi.org/10.3390/brainsci10040232
  42. Ariel J. Kuhn, Jevgenij Raskatov, . Is the p3 Peptide (Aβ17-40, Aβ17-42) Relevant to the Pathology of Alzheimer’s Disease?1. Journal of Alzheimer's Disease 2020, 74 (1) , 43-53. https://doi.org/10.3233/JAD-191201
  43. Pei‐Ning Wang, Kun‐Ju Lin, Huei‐Chun Liu, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Shieh‐Yueh Yang. Plasma pyroglutamate‐modified amyloid beta differentiates amyloid pathology. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring 2020, 12 (1) https://doi.org/10.1002/dad2.12029
  44. Sharon C. Yates, Nicolaas E. Groeneboom, Christopher Coello, Stefan F. Lichtenthaler, Peer-Hendrik Kuhn, Hans-Ulrich Demuth, Maike Hartlage-Rübsamen, Steffen Roßner, Trygve Leergaard, Anna Kreshuk, Maja A. Puchades, Jan G. Bjaalie. QUINT: Workflow for Quantification and Spatial Analysis of Features in Histological Images From Rodent Brain. Frontiers in Neuroinformatics 2019, 13 https://doi.org/10.3389/fninf.2019.00075
  45. Oliver Wirths, Silvia Zampar. Emerging roles of N- and C-terminally truncated Aβ species in Alzheimer’s disease. Expert Opinion on Therapeutic Targets 2019, 23 (12) , 991-1004. https://doi.org/10.1080/14728222.2019.1702972
  46. , Oliver Wirths, Silvia Zampar, , Sascha Weggen, . N-Terminally Truncated Aß Peptide Variants in Alzheimer’s Disease. 2019,,, 107-122. https://doi.org/10.15586/alzheimersdisease.2019.ch7
  47. Ran Nie, Zhou Wu, Junjun Ni, Fan Zeng, Weixian Yu, Yufeng Zhang, Tomoko Kadowaki, Haruhiko Kashiwazaki, Jessica L. Teeling, Yanmin Zhou, . Porphyromonas gingivalis Infection Induces Amyloid-β Accumulation in Monocytes/Macrophages. Journal of Alzheimer's Disease 2019, 72 (2) , 479-494. https://doi.org/10.3233/JAD-190298
  48. Xiaojuan Wang, Li Wang, Xi Yu, Yue Li, Zhigang Liu, Yongdong Zou, Yizhi Zheng, Zhendan He, Haiqiang Wu. Glutaminyl cyclase inhibitor exhibits anti-inflammatory effects in both AD and LPS-induced inflammatory model mice. International Immunopharmacology 2019, 75 , 105770. https://doi.org/10.1016/j.intimp.2019.105770
  49. Ana Xu, Feng He, Chenggong Yu, Ying Qu, Qiuqiong Zhang, Jiahui Lv, Xiangna Zhang, Yingying Ran, Chao Wei, Jingde Wu. The Development of Small Molecule Inhibitors of Glutaminyl Cyclase and Isoglutaminyl Cyclase for Alzheimer's Disease. ChemistrySelect 2019, 4 (35) , 10591-10600. https://doi.org/10.1002/slct.201902852
  50. Dileep K. Vijayan, Kam Y.J. Zhang. Human glutaminyl cyclase: Structure, function, inhibitors and involvement in Alzheimer’s disease. Pharmacological Research 2019, 147 , 104342. https://doi.org/10.1016/j.phrs.2019.104342
  51. Nady Braidy, Martin Zarka, Bat-Erdene Jugder, Jeffrey Welch, Tharusha Jayasena, Daniel K. Y. Chan, Perminder Sachdev, Wallace Bridge. The Precursor to Glutathione (GSH), γ-Glutamylcysteine (GGC), Can Ameliorate Oxidative Damage and Neuroinflammation Induced by Aβ40 Oligomers in Human Astrocytes. Frontiers in Aging Neuroscience 2019, 11 https://doi.org/10.3389/fnagi.2019.00177
  52. Michael C. Owen, David Gnutt, Mimi Gao, Sebastian K. T. S. Wärmländer, Jüri Jarvet, Astrid Gräslund, Roland Winter, Simon Ebbinghaus, Birgit Strodel. Effects of in vivo conditions on amyloid aggregation. Chemical Society Reviews 2019, 48 (14) , 3946-3996. https://doi.org/10.1039/C8CS00034D
  53. Xi Yu, Yue Li, Yongdong Zou, Yizhi Zheng, Zhendan He, Zhigang Liu, Wenlin Xie, Haiqiang Wu. Glutaminyl cyclase inhibitor contributes to the regulation of HSP70, HSP90, actin, and ribosome on gene and protein levels in vitro. Journal of Cellular Biochemistry 2019, 120 (6) , 9460-9471. https://doi.org/10.1002/jcb.28222
  54. Weicong Lin, Xiaojie Zheng, Danqing Fang, Shengfu Zhou, Wenjuan Wu, Kangcheng Zheng. Identifying hQC Inhibitors of Alzheimer’s Disease by Effective Customized Pharmacophore-Based Virtual Screening, Molecular Dynamic Simulation, and Binding Free Energy Analysis. Applied Biochemistry and Biotechnology 2019, 187 (4) , 1173-1192. https://doi.org/10.1007/s12010-018-2780-9
  55. Sarah Schemmert, Elena Schartmann, Dominik Honold, Christian Zafiu, Tamar Ziehm, Karl-Josef Langen, Nadim Joni Shah, Janine Kutzsche, Antje Willuweit, Dieter Willbold. Deceleration of the neurodegenerative phenotype in pyroglutamate-Aβ accumulating transgenic mice by oral treatment with the Aβ oligomer eliminating compound RD2. Neurobiology of Disease 2019, 124 , 36-45. https://doi.org/10.1016/j.nbd.2018.10.021
  56. Katiuscia Pagano, Denise Galante, Cristina D’Arrigo, Alessandro Corsaro, Mario Nizzari, Tullio Florio, Henriette Molinari, Simona Tomaselli, Laura Ragona. Effects of Prion Protein on Aβ42 and Pyroglutamate-Modified AβpΕ3-42 Oligomerization and Toxicity. Molecular Neurobiology 2019, 56 (3) , 1957-1971. https://doi.org/10.1007/s12035-018-1202-x
  57. Ana-María Lacosta, María Pascual-Lucas, Pedro Pesini, Diego Casabona, Virginia Pérez-Grijalba, Iván Marcos-Campos, Leticia Sarasa, Jesus Canudas, Hassnae Badi, Inmaculada Monleón, Itziar San-José, Josep Munuera, Octavio Rodríguez-Gómez, Carla Abdelnour, Asunción Lafuente, Mar Buendía, Mercè Boada, Lluis Tárraga, Agustín Ruiz, Manuel Sarasa. Safety, tolerability and immunogenicity of an active anti-Aβ40 vaccine (ABvac40) in patients with Alzheimer’s disease: a randomised, double-blind, placebo-controlled, phase I trial. Alzheimer's Research & Therapy 2018, 10 (1) https://doi.org/10.1186/s13195-018-0340-8
  58. Olga Pletnikova, Yusuke Kageyama, Gay Rudow, Katherine D. LaClair, Marilyn Albert, Barbara J. Crain, Jing Tian, David Fowler, Juan C. Troncoso. The spectrum of preclinical Alzheimer's disease pathology and its modulation by ApoE genotype. Neurobiology of Aging 2018, 71 , 72-80. https://doi.org/10.1016/j.neurobiolaging.2018.07.007
  59. Julie Dunys, Audrey Valverde, Frédéric Checler. Are N- and C-terminally truncated Aβ species key pathological triggers in Alzheimer's disease?. Journal of Biological Chemistry 2018, 293 (40) , 15419-15428. https://doi.org/10.1074/jbc.R118.003999
  60. Gerhard Rammes, Franziska Seeser, Korinna Mattusch, Kaichuan Zhu, Laura Haas, Markus Kummer, Michael Heneka, Jochen Herms, Chris G. Parsons. The NMDA receptor antagonist Radiprodil reverses the synaptotoxic effects of different amyloid-beta (Aβ) species on long-term potentiation (LTP). Neuropharmacology 2018, 140 , 184-192. https://doi.org/10.1016/j.neuropharm.2018.07.021
  61. Sami Abu Hamdeh, Erik Rollman Waara, Christer Möller, Linda Söderberg, Hans Basun, Irina Alafuzoff, Lars Hillered, Lars Lannfelt, Martin Ingelsson, Niklas Marklund. Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury. Brain Pathology 2018, 28 (4) , 451-462. https://doi.org/10.1111/bpa.12532
  62. Stephan Schilling, Jens-Ulrich Rahfeld, Inge Lues, Cynthia Lemere. Passive Aβ Immunotherapy: Current Achievements and Future Perspectives. Molecules 2018, 23 (5) , 1068. https://doi.org/10.3390/molecules23051068
  63. Pankaj D. Mehta, Bruce A. Patrick, Marc Barshatzky, Sangita P. Mehta, Janusz Frackowiak, Bozena Mazur-Kolecka, Jerzy Wegiel, Thomas Wisniewski, David L. Miller. Generation and Partial Characterization of Rabbit Monoclonal Antibody to Pyroglutamate Amyloid-β3-42 (pE3-Aβ). Journal of Alzheimer's Disease 2018, 62 (4) , 1635-1649. https://doi.org/10.3233/JAD-170898
  64. Jose S. Lopez-Noguerola, Nicolai M. E. Giessen, Maximilian Ueberück, Julius N. Meißner, Charlotte E. Pelgrim, Johnathan Adams, Oliver Wirths, Yvonne Bouter, Thomas A. Bayer. Synergistic Effect on Neurodegeneration by N-Truncated Aβ4−42 and Pyroglutamate Aβ3−42 in a Mouse Model of Alzheimer's Disease. Frontiers in Aging Neuroscience 2018, 10 https://doi.org/10.3389/fnagi.2018.00064
  65. Alvard Antonyan, Dagmar Schlenzig, Stephan Schilling, Marcel Naumann, Svetlana Sharoyan, Sona Mardanyan, Hans-Ulrich Demuth. Concerted action of dipeptidyl peptidase IV and glutaminyl cyclase results in formation of pyroglutamate-modified amyloid peptides in vitro. Neurochemistry International 2018, 113 , 112-119. https://doi.org/10.1016/j.neuint.2017.12.001
  66. Valentina Borghesani, Bruno Alies, Christelle Hureau. Cu II Binding to Various Forms of Amyloid‐β Peptides: Are They Friends or Foes?. European Journal of Inorganic Chemistry 2018, 2018 (1) , 7-15. https://doi.org/10.1002/ejic.201700776
  67. Leo Tsuda, Young-Mi Lim. Alzheimer’s Disease Model System Using Drosophila. 2018,,, 25-40. https://doi.org/10.1007/978-981-13-0529-0_3
  68. Leo Tsuda, Yasuhiro Omata, Yasutoyo Yamasaki, Ryunosuke Minami, Young-Mi Lim. Pyroglutamate–amyloid-β peptide expression in Drosophila leads to caspase-dependent and endoplasmic reticulum stress–related progressive neurodegeneration. Human Molecular Genetics 2017, 26 (23) , 4642-4656. https://doi.org/10.1093/hmg/ddx346
  69. Alex E. Roher, Tyler A. Kokjohn, Steven G. Clarke, Michael R. Sierks, Chera L. Maarouf, Geidy E. Serrano, Marwan S. Sabbagh, Thomas G. Beach. APP/Aβ structural diversity and Alzheimer's disease pathogenesis. Neurochemistry International 2017, 110 , 1-13. https://doi.org/10.1016/j.neuint.2017.08.007
  70. Claudia Spahn, Michael Wermann, Rico Eichentopf, Gerd Hause, Dagmar Schlenzig, Stephan Schilling. Purification of recombinant Aβ(1-42) and pGlu-Aβ(3-42) using preparative SDS-PAGE. ELECTROPHORESIS 2017, 38 (16) , 2042-2049. https://doi.org/10.1002/elps.201700154
  71. Anke Piechotta, Christoph Parthier, Martin Kleinschmidt, Kathrin Gnoth, Thierry Pillot, Inge Lues, Hans-Ulrich Demuth, Stephan Schilling, Jens-Ulrich Rahfeld, Milton T. Stubbs. Structural and functional analyses of pyroglutamate-amyloid-β-specific antibodies as a basis for Alzheimer immunotherapy. Journal of Biological Chemistry 2017, 292 (30) , 12713-12724. https://doi.org/10.1074/jbc.M117.777839
  72. Katarzyna M Grochowska, PingAn Yuanxiang, Julia Bär, Rajeev Raman, Gemma Brugal, Giriraj Sahu, Michaela Schweizer, Arthur Bikbaev, Stephan Schilling, Hans‐Ulrich Demuth, Michael R Kreutz. Posttranslational modification impact on the mechanism by which amyloid‐β induces synaptic dysfunction. EMBO reports 2017, 18 (6) , 962-981. https://doi.org/10.15252/embr.201643519
  73. Chris G. Parsons, Gerhard Rammes. Preclinical to phase II amyloid beta (A β ) peptide modulators under investigation for Alzheimer’s disease. Expert Opinion on Investigational Drugs 2017, 26 (5) , 579-592. https://doi.org/10.1080/13543784.2017.1313832
  74. Greg Goldblatt, Lucia Cilenti, Jason O. Matos, Briana Lee, Nicholas Ciaffone, Qing X. Wang, Laurene Tetard, Ken Teter, Suren A. Tatulian. Unmodified and pyroglutamylated amyloid β peptides form hypertoxic hetero‐oligomers of unique secondary structure. The FEBS Journal 2017, 284 (9) , 1355-1369. https://doi.org/10.1111/febs.14058
  75. Christina Dammers, Kerstin Reiss, Lothar Gremer, Justin Lecher, Tamar Ziehm, Matthias Stoldt, Melanie Schwarten, Dieter Willbold. Pyroglutamate-Modified Amyloid-β(3–42) Shows α-Helical Intermediates before Amyloid Formation. Biophysical Journal 2017, 112 (8) , 1621-1633. https://doi.org/10.1016/j.bpj.2017.03.007
  76. Paulina R. Davis, Ginevra Giannini, Karin Rudolph, Nathaniel Calloway, Christopher M. Royer, Tina L. Beckett, M. Paul Murphy, Frederick Bresch, Dieter Pagani, Thomas Platt, Xiaohong Wang, Amy Skinner Donovan, Tiffany L. Sudduth, Wenjie Lou, Erin Abner, Richard Kryscio, Donna M. Wilcock, Edward G. Barrett, Elizabeth Head. Aβ vaccination in combination with behavioral enrichment in aged beagles: effects on cognition, Aβ, and microhemorrhages. Neurobiology of Aging 2017, 49 , 86-99. https://doi.org/10.1016/j.neurobiolaging.2016.09.007
  77. C. Dammers, M. Schwarten, A. K. Buell, D. Willbold. Pyroglutamate-modified Aβ(3-42) affects aggregation kinetics of Aβ(1-42) by accelerating primary and secondary pathways. Chemical Science 2017, 8 (7) , 4996-5004. https://doi.org/10.1039/C6SC04797A
  78. Chiara Lambruschini, Denise Galante, Lisa Moni, Francesco Ferraro, Giulio Gancia, Renata Riva, Alessia Traverso, Luca Banfi, Cristina D'Arrigo. Multicomponent, fragment-based synthesis of polyphenol-containing peptidomimetics and their inhibiting activity on beta-amyloid oligomerization. Organic & Biomolecular Chemistry 2017, 15 (44) , 9331-9351. https://doi.org/10.1039/C7OB02182H
  79. Holger A. Scheidt, Juliane Adler, Martin Krueger, Daniel Huster. Fibrils of Truncated Pyroglutamyl-Modified Aβ Peptide Exhibit a Similar Structure as Wildtype Mature Aβ Fibrils. Scientific Reports 2016, 6 (1) https://doi.org/10.1038/srep33531
  80. Denise Galante, Francesco Simone Ruggeri, Giovanni Dietler, Francesca Pellistri, Elena Gatta, Alessandro Corsaro, Tullio Florio, Angelo Perico, Cristina D’Arrigo. A critical concentration of N-terminal pyroglutamylated amyloid beta drives the misfolding of Ab1-42 into more toxic aggregates. The International Journal of Biochemistry & Cell Biology 2016, 79 , 261-270. https://doi.org/10.1016/j.biocel.2016.08.037
  81. Philipp Spitzer, Mateja Condic, Martin Herrmann, Timo Jan Oberstein, Marina Scharin-Mehlmann, Daniel F. Gilbert, Oliver Friedrich, Teja Grömer, Johannes Kornhuber, Roland Lang, Juan Manuel Maler. Amyloidogenic amyloid-β-peptide variants induce microbial agglutination and exert antimicrobial activity. Scientific Reports 2016, 6 (1) https://doi.org/10.1038/srep32228
  82. James R. Bamburg, Barbara W. Bernstein. Actin dynamics and cofilin-actin rods in alzheimer disease. Cytoskeleton 2016, 73 (9) , 477-497. https://doi.org/10.1002/cm.21282
  83. Robert J. Andrew, Katherine A.B. Kellett, Gopal Thinakaran, Nigel M. Hooper. A Greek Tragedy: The Growing Complexity of Alzheimer Amyloid Precursor Protein Proteolysis. Journal of Biological Chemistry 2016, 291 (37) , 19235-19244. https://doi.org/10.1074/jbc.R116.746032
  84. Jochen Herms, Mario M. Dorostkar. Dendritic Spine Pathology in Neurodegenerative Diseases. Annual Review of Pathology: Mechanisms of Disease 2016, 11 (1) , 221-250. https://doi.org/10.1146/annurev-pathol-012615-044216
  85. Manman Li, Yao Dong, Xi Yu, Yongdong Zou, Yizhi Zheng, Xianzhang Bu, Junmin Quan, Zhendan He, Haiqiang Wu. Inhibitory effect of flavonoids on human glutaminyl cyclase. Bioorganic & Medicinal Chemistry 2016, 24 (10) , 2280-2286. https://doi.org/10.1016/j.bmc.2016.03.064
  86. Melanie Wulff, Monika Baumann, Anka Thümmler, Jay K. Yadav, Liesa Heinrich, Uwe Knüpfer, Dagmar Schlenzig, Angelika Schierhorn, Jens-Ulrich Rahfeld, Uwe Horn, Jochen Balbach, Hans-Ulrich Demuth, Marcus Fändrich. Verstärkte Fibrillen-Fragmentierung N-terminal verkürzter, Pyroglutamat-modifizierter Aβ-Peptide. Angewandte Chemie 2016, 128 (16) , 5165-5168. https://doi.org/10.1002/ange.201511099
  87. Melanie Wulff, Monika Baumann, Anka Thümmler, Jay K. Yadav, Liesa Heinrich, Uwe Knüpfer, Dagmar Schlenzig, Angelika Schierhorn, Jens-Ulrich Rahfeld, Uwe Horn, Jochen Balbach, Hans-Ulrich Demuth, Marcus Fändrich. Enhanced Fibril Fragmentation of N-Terminally Truncated and Pyroglutamyl-Modified Aβ Peptides. Angewandte Chemie International Edition 2016, 55 (16) , 5081-5084. https://doi.org/10.1002/anie.201511099
  88. Adam P. Gunn, Bruce X. Wong, Timothy Johanssen, James C. Griffith, Colin L. Masters, Ashley I. Bush, Kevin J. Barnham, James A. Duce, Robert A. Cherny. Amyloid-β Peptide Aβ3pE-42 Induces Lipid Peroxidation, Membrane Permeabilization, and Calcium Influx in Neurons. Journal of Biological Chemistry 2016, 291 (12) , 6134-6145. https://doi.org/10.1074/jbc.M115.655183
  89. Alex E. Roher, Chera L. Maarouf, Tyler A. Kokjohn. Familial Presenilin Mutations and Sporadic Alzheimer’s Disease Pathology: Is the Assumption of Biochemical Equivalence Justified?. Journal of Alzheimer's Disease 2016, 50 (3) , 645-658. https://doi.org/10.3233/JAD-150757
  90. Thomas A. Bayer, Oliver Wirths. Immunotherapy Against N-Truncated Amyloid-β Oligomers. 2016,,, 37-50. https://doi.org/10.1007/978-1-4939-3560-4_3
  91. H. Crehan, C.A. Lemere. Anti-Amyloid-β Immunotherapy for Alzheimer’s Disease. 2016,,, 193-226. https://doi.org/10.1016/B978-0-12-802173-6.00007-1
  92. Valérie Vingtdeux, Haitian Zhao, Pallavi Chandakkar, Christopher M Acker, Peter Davies, Philippe Marambaud. A Modification-Specific Peptide-Based immunization Approach Using CRM197 Carrier Protein: Development of a Selective Vaccine Against Pyroglutamate Aβ Peptides. Molecular Medicine 2016, 22 (1) , 841-849. https://doi.org/10.2119/molmed.2016.00218
  93. Christina Dammers, Lothar Gremer, Kerstin Reiß, Antonia N. Klein, Philipp Neudecker, Rudolf Hartmann, Na Sun, Hans-Ulrich Demuth, Melanie Schwarten, Dieter Willbold, . Structural Analysis and Aggregation Propensity of Pyroglutamate Aβ(3-40) in Aqueous Trifluoroethanol. PLOS ONE 2015, 10 (11) , e0143647. https://doi.org/10.1371/journal.pone.0143647
  94. Marton Siklos, Manel BenAissa, Gregory R.J. Thatcher. Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors. Acta Pharmaceutica Sinica B 2015, 5 (6) , 506-519. https://doi.org/10.1016/j.apsb.2015.08.001
  95. Joseph D. Barritt, John H. Viles. Truncated Amyloid-β(11–40/42) from Alzheimer Disease Binds Cu2+ with a Femtomolar Affinity and Influences Fiber Assembly. Journal of Biological Chemistry 2015, 290 (46) , 27791-27802. https://doi.org/10.1074/jbc.M115.684084
  96. Christina Dammers, Lothar Gremer, Philipp Neudecker, Hans-Ulrich Demuth, Melanie Schwarten, Dieter Willbold, . Purification and Characterization of Recombinant N-Terminally Pyroglutamate-Modified Amyloid-β Variants and Structural Analysis by Solution NMR Spectroscopy. PLOS ONE 2015, 10 (10) , e0139710. https://doi.org/10.1371/journal.pone.0139710
  97. Xueli Zhang, Yanli Tian, Can Zhang, Xiaoyu Tian, Alana W. Ross, Robert D. Moir, Hongbin Sun, Rudolph E. Tanzi, Anna Moore, Chongzhao Ran. Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease. Proceedings of the National Academy of Sciences 2015, 112 (31) , 9734-9739. https://doi.org/10.1073/pnas.1505420112
  98. Maria Jonson, Malgorzata Pokrzywa, Annika Starkenberg, Per Hammarstrom, Stefan Thor, . Systematic Aβ Analysis in Drosophila Reveals High Toxicity for the 1-42, 3-42 and 11-42 Peptides, and Emphasizes N- and C-Terminal Residues. PLOS ONE 2015, 10 (7) , e0133272. https://doi.org/10.1371/journal.pone.0133272
  99. Mario M. Dorostkar, Chengyu Zou, Lidia Blazquez-Llorca, Jochen Herms. Analyzing dendritic spine pathology in Alzheimer’s disease: problems and opportunities. Acta Neuropathologica 2015, 130 (1) , 1-19. https://doi.org/10.1007/s00401-015-1449-5
  100. Allen F. Brooks, Isaac M. Jackson, Xia Shao, George W. Kropog, Phillip Sherman, Carole A. Quesada, Peter J. H. Scott. Synthesis and evaluation of [ 11 C]PBD150, a radiolabeled glutaminyl cyclase inhibitor for the potential detection of Alzheimer's disease prior to amyloid β aggregation. MedChemComm 2015, 6 (6) , 1065-1068. https://doi.org/10.1039/C5MD00148J
Load all citations

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect

This website uses cookies to improve your user experience. By continuing to use the site, you are accepting our use of cookies. Read the ACS privacy policy.

CONTINUE