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Book ; Online ; Thesis: Charakterisierung von Antikörpern gegen das Pyroglutamat-3-Amyloid-beta Peptid (AβpE3-Peptid) als Voraussetzung für eine potentielle Anwendung in der Alzheimer Immuntherapie

Piechotta, Anke [Verfasser]

2017

Author's details	Anke Piechotta
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Halle ; Universitäts- und Landesbibliothek Sachsen-Anhalt
Publishing place	Saale
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Mammalian-like type II glutaminyl cyclases in Porphyromonas gingivalis and other oral pathogenic bacteria as targets for treatment of periodontitis.

Taudte, Nadine / Linnert, Miriam / Rahfeld, Jens-Ulrich / Piechotta, Anke / Ramsbeck, Daniel / Buchholz, Mirko / Kolenko, Petr / Parthier, Christoph / Houston, John A / Veillard, Florian / Eick, Sigrun / Potempa, Jan / Schilling, Stephan / Demuth, Hans-Ulrich / Stubbs, Milton T

The Journal of biological chemistry

2021

Abstract: The development of a targeted therapy would significantly improve the treatment of periodontitis and its associated diseases including Alzheimer Disease, rheumatoid arthritis, and cardiovascular diseases. Glutaminyl cyclases (QCs) from the oral ... ...

Abstract	The development of a targeted therapy would significantly improve the treatment of periodontitis and its associated diseases including Alzheimer Disease, rheumatoid arthritis, and cardiovascular diseases. Glutaminyl cyclases (QCs) from the oral pathogens
Language	English
Publishing date	2021-01-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA120.016836
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Article ; Online: Development of the clinical candidate PBD-C06, a humanized pGlu3-Aβ-specific antibody against Alzheimer's disease with reduced complement activation.

Hettmann, Thore / Gillies, Stephen D / Kleinschmidt, Martin / Piechotta, Anke / Makioka, Koki / Lemere, Cynthia A / Schilling, Stephan / Rahfeld, Jens-Ulrich / Lues, Inge

Scientific reports

2020 Volume 10, Issue 1, Page(s) 3294

Abstract: In clinical trials with early Alzheimer's patients, administration of anti-amyloid antibodies reduced amyloid deposits, suggesting that immunotherapies may be promising disease-modifying interventions against Alzheimer's disease (AD). Specific forms of ... ...

Abstract	In clinical trials with early Alzheimer's patients, administration of anti-amyloid antibodies reduced amyloid deposits, suggesting that immunotherapies may be promising disease-modifying interventions against Alzheimer's disease (AD). Specific forms of amyloid beta (Aβ) peptides, for example post-translationally modified Aβ peptides with a pyroglutamate at the N-terminus (pGlu3, pE3), are attractive antibody targets, due to pGlu3-Aβ's neo-epitope character and its propensity to form neurotoxic oligomeric aggregates. We have generated a novel anti-pGlu3-Aβ antibody, PBD-C06, which is based on a murine precursor antibody that binds with high specificity to pGlu3-Aβ monomers, oligomers and fibrils, including mixed aggregates of unmodified Aβ and pGlu3-Aβ peptides. PBD-C06 was generated by first grafting the murine antigen binding sequences onto suitable human variable light and heavy chains. Subsequently, the humanized antibody was de-immunized and site-specific mutations were introduced to restore original target binding, to eliminate complement activation and to improve protein stability. PBD-C06 binds with the same specificity and avidity as its murine precursor antibody and elimination of C1q binding did not compromise Fcγ-receptor binding or in vitro phagocytosis. Thus, PBD-C06 was specifically designed to target neurotoxic aggregates and to avoid complement-mediated inflammatory responses, in order to lower the risk for vasogenic edemas in the clinic.
MeSH term(s)	Alleles ; Alzheimer Disease/immunology ; Alzheimer Disease/therapy ; Amyloid beta-Peptides/chemistry ; Animals ; Antibodies, Monoclonal, Humanized/pharmacology ; Complement Activation ; Complement C1q/immunology ; Complementarity Determining Regions ; Edema/prevention & control ; Endocytosis ; Epitopes/chemistry ; Humans ; Immunotherapy ; Inflammation ; Mice ; Mutation ; Phagocytosis ; Protein Binding ; Protein Processing, Post-Translational ; Pyrrolidonecarboxylic Acid/chemistry
Chemical Substances	Amyloid beta-Peptides ; Antibodies, Monoclonal, Humanized ; Complementarity Determining Regions ; Epitopes ; Complement C1q (80295-33-6) ; Pyrrolidonecarboxylic Acid (SZB83O1W42)
Language	English
Publishing date	2020-02-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-60319-5
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Article ; Online: Mammalian-like type II glutaminyl cyclases in Porphyromonas gingivalis and other oral pathogenic bacteria as targets for treatment of periodontitis.

The Journal of biological chemistry

2021 Volume 296, Page(s) 100263

Abstract: The development of a targeted therapy would significantly improve the treatment of periodontitis and its associated diseases including Alzheimer's disease, rheumatoid arthritis, and cardiovascular diseases. Glutaminyl cyclases (QCs) from the oral ... ...

Abstract	The development of a targeted therapy would significantly improve the treatment of periodontitis and its associated diseases including Alzheimer's disease, rheumatoid arthritis, and cardiovascular diseases. Glutaminyl cyclases (QCs) from the oral pathogens Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia represent attractive target enzymes for small-molecule inhibitor development, as their action is likely to stabilize essential periplasmic and outer membrane proteins by N-terminal pyroglutamination. In contrast to other microbial QCs that utilize the so-called type I enzymes, these oral pathogens possess sequences corresponding to type II QCs, observed hitherto only in animals. However, whether differences between these bacteroidal QCs and animal QCs are sufficient to enable development of selective inhibitors is not clear. To learn more, we recombinantly expressed all three QCs. They exhibit comparable catalytic efficiencies and are inhibited by metal chelators. Crystal structures of the enzymes from P. gingivalis (PgQC) and T. forsythia (TfQC) reveal a tertiary structure composed of an eight-stranded β-sheet surrounded by seven α-helices, typical of animal type II QCs. In each case, an active site Zn ion is tetrahedrally coordinated by conserved residues. Nevertheless, significant differences to mammalian enzymes are found around the active site of the bacteroidal enzymes. Application of a PgQC-selective inhibitor described here for the first time results in growth inhibition of two P. gingivalis clinical isolates in a dose-dependent manner. The insights gained by these studies will assist in the development of highly specific small-molecule bacteroidal QC inhibitors, paving the way for alternative therapies against periodontitis and associated diseases.
MeSH term(s)	Aminoacyltransferases/antagonists & inhibitors ; Aminoacyltransferases/chemistry ; Aminoacyltransferases/genetics ; Aminoacyltransferases/ultrastructure ; Catalytic Domain/drug effects ; Crystallography, X-Ray ; Humans ; Periodontitis/drug therapy ; Periodontitis/genetics ; Periodontitis/microbiology ; Porphyromonas gingivalis/enzymology ; Porphyromonas gingivalis/pathogenicity ; Prevotella intermedia/enzymology ; Prevotella intermedia/pathogenicity ; Protein Structure, Tertiary/drug effects ; Pyrrolidonecarboxylic Acid/chemistry ; Pyrrolidonecarboxylic Acid/metabolism ; Tannerella forsythia/enzymology ; Tannerella forsythia/pathogenicity
Chemical Substances	Aminoacyltransferases (EC 2.3.2.-) ; glutaminyl-peptide cyclotransferase (EC 2.3.2.5) ; Pyrrolidonecarboxylic Acid (SZB83O1W42)
Language	English
Publishing date	2021-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2021.100263
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Article ; Online: Development of the clinical candidate PBD-C06, a humanized pGlu3-Av-specific antibody against Alzheimer's disease with reduced complement activation

Hettmann, Thore / Gillies, Stephen D. / Kleinschmidt, Martin / Piechotta, Anke / Makioka, Koki / Lemere, Cynthia A. / Schilling, Stephan / Rahfeld, Jens-Ulrich / Lues, Inge

2020

Abstract: Art. 3294, 13 S. ... In clinical trials with early Alzheimer's patients, administration of anti-amyloid antibodies reduced amyloid deposits, suggesting that immunotherapies may be promising disease-modifying interventions against Alzheimer's disease (AD). ... ...

Abstract	Art. 3294, 13 S. In clinical trials with early Alzheimer's patients, administration of anti-amyloid antibodies reduced amyloid deposits, suggesting that immunotherapies may be promising disease-modifying interventions against Alzheimer's disease (AD). Specific forms of amyloid beta (Av) peptides, for example post-translationally modified Av peptides with a pyroglutamate at the N-terminus (pGlu3, pE3), are attractive antibody targets, due to pGlu3-Av's neo-epitope character and its propensity to form neurotoxic oligomeric aggregates. We have generated a novel anti-pGlu3-Av antibody, PBD-C06, which is based on a murine precursor antibody that binds with high specificity to pGlu3-Av monomers, oligomers and fibrils, including mixed aggregates of unmodified Av and pGlu3-Av peptides. PBD-C06 was generated by first grafting the murine antigen binding sequences onto suitable human variable light and heavy chains. Subsequently, the humanized antibody was de-immunized and site-specific mutations were introduced to restore original target binding, to eliminate complement activation and to improve protein stability. PBD-C06 binds with the same specificity and avidity as its murine precursor antibody and elimination of C1q binding did not compromise Fcg-receptor binding or in vitro phagocytosis. Thus, PBD-C06 was specifically designed to target neurotoxic aggregates and to avoid complement-mediated inflammatory responses, in order to lower the risk for vasogenic edemas in the clinic. 10 Nr.1
Keywords	Alzheimer's disease ; 610 ; 620
Subject code	616 ; 570
Language	English
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Development of the clinical candidate PBD-C06, a humanized pGlu3-Aβ-specific antibody against Alzheimer’s disease with reduced complement activation

Thore Hettmann / Stephen D. Gillies / Martin Kleinschmidt / Anke Piechotta / Koki Makioka / Cynthia A. Lemere / Stephan Schilling / Jens-Ulrich Rahfeld / Inge Lues

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 13

Abstract: Abstract In clinical trials with early Alzheimer’s patients, administration of anti-amyloid antibodies reduced amyloid deposits, suggesting that immunotherapies may be promising disease-modifying interventions against Alzheimer’s disease (AD). Specific ... ...

Abstract	Abstract In clinical trials with early Alzheimer’s patients, administration of anti-amyloid antibodies reduced amyloid deposits, suggesting that immunotherapies may be promising disease-modifying interventions against Alzheimer’s disease (AD). Specific forms of amyloid beta (Aβ) peptides, for example post-translationally modified Aβ peptides with a pyroglutamate at the N-terminus (pGlu3, pE3), are attractive antibody targets, due to pGlu3-Aβ’s neo-epitope character and its propensity to form neurotoxic oligomeric aggregates. We have generated a novel anti-pGlu3-Aβ antibody, PBD-C06, which is based on a murine precursor antibody that binds with high specificity to pGlu3-Aβ monomers, oligomers and fibrils, including mixed aggregates of unmodified Aβ and pGlu3-Aβ peptides. PBD-C06 was generated by first grafting the murine antigen binding sequences onto suitable human variable light and heavy chains. Subsequently, the humanized antibody was de-immunized and site-specific mutations were introduced to restore original target binding, to eliminate complement activation and to improve protein stability. PBD-C06 binds with the same specificity and avidity as its murine precursor antibody and elimination of C1q binding did not compromise Fcγ-receptor binding or in vitro phagocytosis. Thus, PBD-C06 was specifically designed to target neurotoxic aggregates and to avoid complement-mediated inflammatory responses, in order to lower the risk for vasogenic edemas in the clinic.
Keywords	Medicine ; R ; Science ; Q
Subject code	616 ; 570
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models.

Sebastian Monasor, Laura / Müller, Stephan A / Colombo, Alessio Vittorio / Tanrioever, Gaye / König, Jasmin / Roth, Stefan / Liesz, Arthur / Berghofer, Anna / Piechotta, Anke / Prestel, Matthias / Saito, Takashi / Saido, Takaomi C / Herms, Jochen / Willem, Michael / Haass, Christian / Lichtenthaler, Stefan F / Tahirovic, Sabina

eLife

2020 Volume 9

Abstract: Microglial dysfunction is a key pathological feature of Alzheimer's disease (AD), but little is known about proteome-wide changes in microglia during the course of AD and their functional consequences. Here, we performed an in-depth and time-resolved ... ...

Abstract	Microglial dysfunction is a key pathological feature of Alzheimer's disease (AD), but little is known about proteome-wide changes in microglia during the course of AD and their functional consequences. Here, we performed an in-depth and time-resolved proteomic characterization of microglia in two mouse models of amyloid β (Aβ) pathology, the overexpression APPPS1 and the knock-in APP-NL-G-F (APP-KI) model. We identified a large panel of Microglial Aβ Response Proteins (MARPs) that reflect heterogeneity of microglial alterations during early, middle and advanced stages of Aβ deposition and occur earlier in the APPPS1 mice. Strikingly, the kinetic differences in proteomic profiles correlated with the presence of fibrillar Aβ, rather than dystrophic neurites, suggesting that fibrillar Aβ may trigger the AD-associated microglial phenotype and the observed functional decline. The identified microglial proteomic fingerprints of AD provide a valuable resource for functional studies of novel molecular targets and potential biomarkers for monitoring AD progression or therapeutic efficacy.
MeSH term(s)	Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/genetics ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/genetics ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Disease Models, Animal ; Female ; Gene Knock-In Techniques ; Male ; Mice ; Mice, Transgenic ; Microglia/metabolism ; Microglia/pathology ; Proteome/metabolism
Chemical Substances	Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Proteome
Language	English
Publishing date	2020-06-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.54083
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Article ; Online: Mammalian-like type II glutaminyl cyclases in Porphyromonas gingivalis and other oral pathogenic bacteria as targets for treatment of periodontitis

Taudte, Nadine / Linnert, Miriam / Rahfeld, Jens-Ulrich / Piechotta, Anke / Ramsbeck, Daniel / Buchholz, Mirko / Kolenko, Petr / Parthier, Christoph / Houston, John A. / Veillard, Florian / Eick, Sigrun / Potempa, Jan / Schilling, Stephan / Demuth, Hans-Ulrich / Stubbs, Milton T.

2021

Abstract: Art. 100263, 13 S. ... The development of a targeted therapy would significantly improve the treatment of periodontitis and its associated diseases including Alzheimer's disease, rheumatoid arthritis, and cardiovascular diseases. Glutaminyl cyclases (QCs) ... ...

Abstract	Art. 100263, 13 S. The development of a targeted therapy would significantly improve the treatment of periodontitis and its associated diseases including Alzheimer's disease, rheumatoid arthritis, and cardiovascular diseases. Glutaminyl cyclases (QCs) from the oral pathogens Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia represent attractive target enzymes for small-molecule inhibitor development, as their action is likely to stabilize essential periplasmic and outer membrane proteins by N-terminal pyroglutamination. In contrast to other microbial QCs that utilize the so-called type I enzymes, these oral pathogens possess sequences corresponding to type II QCs, observed hitherto only in animals. However, whether differences between these bacteroidal QCs and animal QCs are sufficient to enable development of selective inhibitors is not clear. To learn more, we recombinantly expressed all three QCs. They exhibit comparable catalytic efficiencies and are inhibited by metal chelators. Crystal structures of the enzymes from P. gingivalis (PgQC) and T. forsythia (TfQC) reveal a tertiary structure composed of an eight-stranded v-sheet surrounded by seven a-helices, typical of animal type II QCs. In each case, an active site Zn ion is tetrahedrally coordinated by conserved residues. Nevertheless, significant differences to mammalian enzymes are found around the active site of the bacteroidal enzymes. Application of a PgQC-selective inhibitor described here for the first time results in growth inhibition of two P. gingivalis clinical isolates in a dose-dependent manner. The insights gained by these studies will assist in the development of highly specific small-molecule bacteroidal QC inhibitors, paving the way for alternative therapies against periodontitis and associated diseases. 296
Keywords	Bibliographie ; bacterial pathogens ; crystal structure ; drug design ; enzyme structure ; periodontal disease ; Glutaminyl cyclase ; Porphyromonas gingivalis ; 610 ; 572 ; 620
Subject code	572
Language	English
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Targeting isoaspartate-modified Aβ rescues behavioral deficits in transgenic mice with Alzheimer's disease-like pathology.

Gnoth, Kathrin / Piechotta, Anke / Kleinschmidt, Martin / Konrath, Sandra / Schenk, Mathias / Taudte, Nadine / Ramsbeck, Daniel / Rieckmann, Vera / Geissler, Stefanie / Eichentopf, Rico / Barendrecht, Susan / Hartlage-Rübsamen, Maike / Demuth, Hans-Ulrich / Roßner, Steffen / Cynis, Holger / Rahfeld, Jens-Ulrich / Schilling, Stephan

Alzheimer's research & therapy

2020 Volume 12, Issue 1, Page(s) 149

Abstract: Background: Amyloid β (Aβ)-directed immunotherapy has shown promising results in preclinical and early clinical Alzheimer's disease (AD) trials, but successful translation to late clinics has failed so far. Compelling evidence suggests that post- ... ...

Abstract	Background: Amyloid β (Aβ)-directed immunotherapy has shown promising results in preclinical and early clinical Alzheimer's disease (AD) trials, but successful translation to late clinics has failed so far. Compelling evidence suggests that post-translationally modified Aβ peptides might play a decisive role in onset and progression of AD and first clinical trials targeting such Aβ variants have been initiated. Modified Aβ represents a small fraction of deposited material in plaques compared to pan-Aβ epitopes, opening up pathways for tailored approaches of immunotherapy. Here, we generated the first monoclonal antibodies that recognize L-isoaspartate-modified Aβ (isoD7-Aβ) and tested a lead antibody molecule in 5xFAD mice. Methods: This work comprises a combination of chemical and biochemical techniques as well as behavioral analyses. Aβ peptides, containing L-isoaspartate at position 7, were chemically synthesized and used for immunization of mice and antibody screening methods. Biochemical methods included anti-isoD7-Aβ monoclonal antibody characterization by surface plasmon resonance, immunohistochemical staining of human and transgenic mouse brain, and the development and application of isoD7-Aβ ELISA as well as different non-modified Aβ ELISA. For antibody treatment studies, 12 mg/kg anti-isoD7-Aβ antibody K11_IgG2a was applied intraperitoneally to 5xFAD mice for 38 weeks. Treatment controls implemented were IgG2a isotype as negative and 3D6_IgG2a, the parent molecule of bapineuzumab, as positive control antibodies. Behavioral studies included elevated plus maze, pole test, and Morris water maze. Results: Our advanced antibody K11 showed a K Conclusions: The present study demonstrates, for the first time, that the antibody-mediated targeting of isoD7-modified Aβ peptides leads to attenuation of AD-like amyloid pathology. In conjunction with previously published data on antibodies directed against pGlu-modified Aβ, the results highlight the crucial role of modified Aβ peptides in AD pathophysiology. Hence, the results also underscore the therapeutic potential of targeting modified amyloid species for defining tailored approaches in AD therapy.
MeSH term(s)	Alzheimer Disease/drug therapy ; Alzheimer Disease/genetics ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/genetics ; Animals ; Disease Models, Animal ; Isoaspartic Acid ; Mice ; Mice, Transgenic
Chemical Substances	Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Isoaspartic Acid
Language	English
Publishing date	2020-11-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-020-00719-x
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Article ; Online: Immunohistochemical Evidence from APP-Transgenic Mice for Glutaminyl Cyclase as Drug Target to Diminish pE-Abeta Formation.

Hartlage-Rübsamen, Maike / Bluhm, Alexandra / Piechotta, Anke / Linnert, Miriam / Rahfeld, Jens-Ulrich / Demuth, Hans-Ulrich / Lues, Inge / Kuhn, Peer-Hendrik / Lichtenthaler, Stefan F / Roßner, Steffen / Höfling, Corinna

Molecules (Basel, Switzerland)

2018 Volume 23, Issue 4

Abstract: Oligomeric assemblies of neurotoxic amyloid beta (Abeta) peptides generated by proteolytical processing of the amyloid precursor protein (APP) play a key role in the pathogenesis of Alzheimer’s disease (AD). In recent years, a substantial heterogeneity ... ...

Abstract	Oligomeric assemblies of neurotoxic amyloid beta (Abeta) peptides generated by proteolytical processing of the amyloid precursor protein (APP) play a key role in the pathogenesis of Alzheimer’s disease (AD). In recent years, a substantial heterogeneity of Abeta peptides with distinct biophysical and cell biological properties has been demonstrated. Among these, a particularly neurotoxic and disease-specific Abeta variant is N-terminally truncated and modified to pyroglutamate (pE-Abeta). Cell biological and animal experimental studies imply the catalysis of this modification by the enzyme glutaminyl cyclase (QC). However, direct histopathological evidence in transgenic animals from comparative brain region and cell type-specific expression of transgenic hAPP and QC, on the one hand, and on the formation of pE-Abeta aggregates, on the other, is lacking. Here, using single light microscopic, as well as triple immunofluorescent, labeling, we report the deposition of pE-Abeta only in the brain regions of APP-transgenic Tg2576 mice with detectable human APP and endogenous QC expression, such as the hippocampus, piriform cortex, and amygdala. Brain regions showing human APP expression without the concomitant presence of QC (the anterodorsal thalamic nucleus and perifornical nucleus) do not display pE-Abeta plaque formation. However, we also identified brain regions with substantial expression of human APP and QC in the absence of pE-Abeta deposition (the Edinger-Westphal nucleus and locus coeruleus). In these brain regions, the enzymes required to generate N-truncated Abeta peptides as substrates for QC might be lacking. Our observations provide additional evidence for an involvement of QC in AD pathogenesis via QC-catalyzed pE-Abeta formation.
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Aminoacyltransferases/genetics ; Aminoacyltransferases/metabolism ; Amyloid beta-Peptides/genetics ; Amyloid beta-Peptides/metabolism ; Animals ; Goats ; Humans ; Immunohistochemistry ; Mice ; Models, Animal ; Pyrrolidonecarboxylic Acid/metabolism ; Rats
Chemical Substances	Amyloid beta-Peptides ; Aminoacyltransferases (EC 2.3.2.-) ; glutaminyl-peptide cyclotransferase (EC 2.3.2.5) ; Pyrrolidonecarboxylic Acid (SZB83O1W42)
Language	English
Publishing date	2018-04-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules23040924
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