LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 17

Search options

  1. Article ; Online: Alanine-to-threonine substitutions and amyloid diseases: butyrylcholinesterase as a case study.

    Podoly, Erez / Hanin, Geula / Soreq, Hermona

    Chemico-biological interactions

    2010  Volume 187, Issue 1-3, Page(s) 64–71

    Abstract: Alanine-to-threonine (A to T) substitutions caused by single nucleotide polymorphisms (SNPs) occur in diverse proteins, and in certain cases these substitutions induce self-aggregation into amyloid fibrils or aggregation in other amyloidogenic proteins. ... ...

    Abstract Alanine-to-threonine (A to T) substitutions caused by single nucleotide polymorphisms (SNPs) occur in diverse proteins, and in certain cases these substitutions induce self-aggregation into amyloid fibrils or aggregation in other amyloidogenic proteins. This is compatible with the inverse preferences of alanine to form helices and of threonine to support beta-sheet structures, which are crucial for amyloid fibrils formation. Our interest in these mutations was initiated by studying the potential effects of the A539T substitution in the butyrylcholinesterase BChE-K variant on amyloid fibrils formation in Alzheimer's disease. Other examples are, Parkinson's disease (PD), where A53T alpha-synuclein occurs in Lewy bodies and familial amyloid polyneuropathy (FAP), where an A25T substitution appears in transthyretin (TTR). In peripheral organs, an A34T substitution is found in the light chain immunoglobulin genes of patients with systemic amyloidosis and in familial hypercholesterolemia, an A370T substitution occurs in the LDLR regulator of cholesterol homeostasis. That such substitutions appear in proteins with important cellular functions suggests that they confer antagonistic pleiotropy, providing added value at an earlier age but causing damages and inducing amyloid diseases later on. This, in turn, may explain the evolutionary selection and preservation of these substitutions. The structural effect of residue substitutions and in particular A to T substitutions in amyloidogenic diseases thus merits further attention.
    MeSH term(s) Alanine/genetics ; Alanine/metabolism ; Amino Acid Substitution ; Amyloidosis/enzymology ; Amyloidosis/genetics ; Amyloidosis/metabolism ; Animals ; Butyrylcholinesterase/chemistry ; Butyrylcholinesterase/genetics ; Butyrylcholinesterase/metabolism ; Disease/genetics ; Humans ; Threonine/genetics ; Threonine/metabolism
    Chemical Substances Threonine (2ZD004190S) ; Butyrylcholinesterase (EC 3.1.1.8) ; Alanine (OF5P57N2ZX)
    Language English
    Publishing date 2010-09-06
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 218799-1
    ISSN 1872-7786 ; 0009-2797
    ISSN (online) 1872-7786
    ISSN 0009-2797
    DOI 10.1016/j.cbi.2010.01.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 686: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article: SC35 promotes sustainable stress-induced alternative splicing of neuronal acetylcholinesterase mRNA.

    Meshorer, E / Bryk, B / Toiber, D / Cohen, J / Podoly, E / Dori, A / Soreq, H

    Molecular psychiatry

    2005  Volume 10, Issue 11, Page(s) 985–997

    Abstract: Long-lasting alternative splicing of neuronal acetylcholinesterase (AChE) pre-mRNA occurs during neuronal development and following stress, altering synaptic properties. To explore the corresponding molecular events, we sought to identify mRNAs encoding ... ...

    Abstract Long-lasting alternative splicing of neuronal acetylcholinesterase (AChE) pre-mRNA occurs during neuronal development and following stress, altering synaptic properties. To explore the corresponding molecular events, we sought to identify mRNAs encoding for abundant splicing factors in the prefrontal cortex (PFC) following stress. Here we show elevated levels of the splicing factor SC35 in stressed as compared with naïve mice. In cotransfections of COS-1 and HEK293 cells with an AChE minigene allowing 3' splice variations, SC35 facilitated a shift from the primary AChE-S to the stress-induced AChE-R variant, while ASF/SF2 caused the opposite effect. Transfection with chimeric constructs comprising of SC35 and ASF/SF2 RRM/RS domains identified the SC35 RRM as responsible for AChE mRNA's alternative splicing. In poststress PFC neurons, increased SC35 mRNA and protein levels coincided with selective increase in AChE-R mRNA. In the developing mouse embryo, cortical progenitor cells in the ventricular zone displayed transient SC35 elevation concomitant with dominance of AChE-R over AChE-S mRNA. Finally, transgenic mice overexpressing human AChE-R, but not those overexpressing AChE-S, showed significant elevation in neuronal SC35 levels, suggesting a reciprocal reinforcement process. Together, these findings point to an interactive relationship of SC35 with cholinergic signals in the long-lasting consequences of stress on nervous system plasticity and development.
    MeSH term(s) Acetylcholinesterase/genetics ; Alternative Splicing ; Amino Acid Sequence ; Animals ; Base Sequence ; COS Cells ; Cell Line ; Cercopithecus aethiops ; Female ; Humans ; Male ; Mice ; Molecular Sequence Data ; Neurons/metabolism ; Nuclear Proteins/metabolism ; Pregnancy ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Recombinant Proteins/genetics ; Ribonucleoproteins/metabolism ; Sequence Homology, Amino Acid ; Serine-Arginine Splicing Factors ; Stress, Physiological/genetics ; Stress, Physiological/metabolism ; Transfection
    Chemical Substances Nuclear Proteins ; RNA, Messenger ; Recombinant Proteins ; Ribonucleoproteins ; Sfrs2 protein, mouse ; Serine-Arginine Splicing Factors (170974-22-8) ; Acetylcholinesterase (EC 3.1.1.7)
    Language English
    Publishing date 2005-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1330655-8
    ISSN 1476-5578 ; 1359-4184
    ISSN (online) 1476-5578
    ISSN 1359-4184
    DOI 10.1038/sj.mp.4001735
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4812: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article: RACK1 has the nerve to act: structure meets function in the nervous system.

    Sklan, Ella H / Podoly, Erez / Soreq, Hermona

    Progress in neurobiology

    2006  Volume 78, Issue 2, Page(s) 117–134

    Abstract: The receptor for activated protein kinase C 1 (RACK1) is an intracellular adaptor protein. Accumulating evidence attributes to this member of the tryptophan-aspartate (WD) repeat family the role of regulating several major nervous system pathways. ... ...

    Abstract The receptor for activated protein kinase C 1 (RACK1) is an intracellular adaptor protein. Accumulating evidence attributes to this member of the tryptophan-aspartate (WD) repeat family the role of regulating several major nervous system pathways. Structurally, RACK1 is a seven-bladed-beta-propeller, interacting with diverse proteins having distinct structural folds. When bound to the IP3 receptor, RACK1 regulates intracellular Ca2+ levels, potentially contributing to processes such as learning, memory and synaptic plasticity. By binding to the NMDA receptor, it dictates neuronal excitation and sensitivity to ethanol. When bound to the stress-induced acetylcholinesterase variant AChE-R, RACK1 is implicated in stress responses and behavior, compatible with reports of RACK1 modulations in brain ageing and in various neurodegenerative diseases. This review sheds new light on both the virtues and the variety of neuronal RACK1 interactions and their physiological consequences.
    MeSH term(s) Animals ; Calcium/metabolism ; Calcium Channels/physiology ; GTP-Binding Proteins/chemistry ; GTP-Binding Proteins/physiology ; Humans ; Inositol 1,4,5-Trisphosphate Receptors ; Models, Biological ; Models, Molecular ; Neoplasm Proteins/chemistry ; Neoplasm Proteins/physiology ; Nervous System/cytology ; Nervous System/metabolism ; Neurons/metabolism ; Protein Binding ; Protein Kinase C/metabolism ; Protein Structure, Tertiary ; Receptors for Activated C Kinase ; Receptors, Cell Surface/chemistry ; Receptors, Cell Surface/physiology ; Receptors, Cytoplasmic and Nuclear/physiology
    Chemical Substances Calcium Channels ; ITPR1 protein, human ; Inositol 1,4,5-Trisphosphate Receptors ; Neoplasm Proteins ; RACK1 protein, human ; Receptors for Activated C Kinase ; Receptors, Cell Surface ; Receptors, Cytoplasmic and Nuclear ; Protein Kinase C (EC 2.7.11.13) ; GTP-Binding Proteins (EC 3.6.1.-) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2006-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 185535-9
    ISSN 1873-5118 ; 0301-0082
    ISSN (online) 1873-5118
    ISSN 0301-0082
    DOI 10.1016/j.pneurobio.2005.12.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Se 205: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article: Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility.

    Mor, I / Sklan, E H / Podoly, E / Pick, M / Kirschner, M / Yogev, L / Bar-Sheshet Itach, S / Schreiber, L / Geyer, B / Mor, T / Grisaru, D / Soreq, H

    Journal of cellular and molecular medicine

    2008  Volume 12, Issue 2, Page(s) 479–495

    Abstract: Changes in protein subdomains through alternative splicing often modify protein-protein interactions, altering biological processes. A relevant example is that of the stress-induced up-regulation of the acetylcholinesterase (AChE-R) splice variant, a ... ...

    Abstract Changes in protein subdomains through alternative splicing often modify protein-protein interactions, altering biological processes. A relevant example is that of the stress-induced up-regulation of the acetylcholinesterase (AChE-R) splice variant, a common response in various tissues. In germ cells of male transgenic TgR mice, AChE-R excess associates with reduced sperm differentiation and sperm counts. To explore the mechanism(s) by which AChE-R up-regulation affects spermatogenesis, we identified AChE-R's protein partners through a yeast two-hybrid screen. In meiotic spermatocytes from TgR mice, we detected AChE-R interaction with the scaffold protein RACK1 and elevated apoptosis. This correlated with reduced scavenging by RACK1 of the pro-apoptotic TAp73, an outcome compatible with the increased apoptosis. In contrast, at later stages in sperm development, AChE-R's interaction with the glycolytic enzyme enolase-alpha elevates enolase activity. In transfected cells, enforced AChE-R excess increased glucose uptake and adenosine tri-phosphate (ATP) levels. Correspondingly, TgR sperm cells display elevated ATP levels, mitochondrial hyperactivity and increased motility. In human donors' sperm, we found direct association of sperm motility with AChE-R expression. Interchanging interactions with RACK1 and enolase-alpha may hence enable AChE-R to affect both sperm differentiation and function by participating in independent cellular pathways.
    MeSH term(s) Acetylcholinesterase/genetics ; Acetylcholinesterase/metabolism ; Alternative Splicing ; Animals ; Apoptosis/genetics ; Biopsy ; Humans ; Immunohistochemistry ; Male ; Mice ; Mice, Transgenic ; Models, Biological ; Sperm Motility/genetics ; Spermatozoa/cytology ; Spermatozoa/enzymology ; Spermatozoa/physiology ; Testis/cytology ; Testis/enzymology ; Testis/metabolism ; Testis/physiology ; Testis/surgery
    Chemical Substances Acetylcholinesterase (EC 3.1.1.7)
    Language English
    Publishing date 2008-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2074559-X
    ISSN 1582-4934 ; 1582-1838 ; 1582-4934
    ISSN (online) 1582-4934
    ISSN 1582-1838 ; 1582-4934
    DOI 10.1111/j.1582-4934.2008.00231.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5752: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Human recombinant butyrylcholinesterase purified from the milk of transgenic goats interacts with beta-amyloid fibrils and suppresses their formation in vitro.

    Podoly, E / Bruck, T / Diamant, S / Melamed-Book, N / Weiss, A / Huang, Y / Livnah, O / Langermann, S / Wilgus, H / Soreq, H

    Neuro-degenerative diseases

    2008  Volume 5, Issue 3-4, Page(s) 232–236

    Abstract: Background: In Alzheimer's disease (AD), brain butyrylcholinesterase (BChE) co-localizes with beta-amyloid (Abeta) fibrils.: Aims: In vitro testing of the significance of this phenomenon to AD progress.: Methods: A thioflavine T (ThT) fluorogenic ... ...

    Abstract Background: In Alzheimer's disease (AD), brain butyrylcholinesterase (BChE) co-localizes with beta-amyloid (Abeta) fibrils.
    Aims: In vitro testing of the significance of this phenomenon to AD progress.
    Methods: A thioflavine T (ThT) fluorogenic assay, photo-induced cross-linking and quantifiable electron microscopy served to compare the effect on Abeta fibril formation induced by highly purified recombinant human BChE (rBChE) produced in the milk of transgenic goats with that of serum-derived human BChE.
    Results: Both proteins at 1:50 and 1:25 ratios to Abeta dose-dependently prolonged the ThT lag time and reduced the apparent rate of Abeta fibril formation compared to Abeta alone. Photo-induced cross-linking tests showed that rBChE prolonged the persistence of amyloid dimers, trimers and tetramers in solution, whereas Abeta alone facilitated precipitation of such multimers from solution. Transmission electron microscopy showed that rBChE at 1:100 to Abeta prevented the formation of larger, over 150-nm-long, Abeta fibrils and reduced fibril branching compared to Abeta alone as quantified by macro programming of Image Pro Plus software.
    Conclusion: Our findings demonstrate that rBChE interacts with Abeta fibrils and can attenuate their formation, extension and branching, suggesting further tests of rBChE, with unlimited supply and no associated health risks, as a therapeutic agent for delaying the formation of amyloid toxic oligomers in AD patients.
    MeSH term(s) Amyloid/genetics ; Amyloid/metabolism ; Amyloid beta-Peptides/antagonists & inhibitors ; Amyloid beta-Peptides/genetics ; Amyloid beta-Peptides/metabolism ; Animals ; Animals, Genetically Modified ; Butyrylcholinesterase/genetics ; Butyrylcholinesterase/isolation & purification ; Butyrylcholinesterase/metabolism ; Butyrylcholinesterase/physiology ; Female ; Goats ; Humans ; Milk/enzymology ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism
    Chemical Substances Amyloid ; Amyloid beta-Peptides ; Recombinant Proteins ; Butyrylcholinesterase (EC 3.1.1.8)
    Language English
    Publishing date 2008
    Publishing country Switzerland
    Document type Comparative Study ; Journal Article
    ZDB-ID 2143569-8
    ISSN 1660-2862 ; 1660-2854
    ISSN (online) 1660-2862
    ISSN 1660-2854
    DOI 10.1159/000113711
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5918: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 567: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article: Butyrylcholinesterase attenuates amyloid fibril formation in vitro.

    Diamant, Sophia / Podoly, Erez / Friedler, Assaf / Ligumsky, Hagai / Livnah, Oded / Soreq, Hermona

    Proceedings of the National Academy of Sciences of the United States of America

    2006  Volume 103, Issue 23, Page(s) 8628–8633

    Abstract: In Alzheimer's disease, both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) colocalize with brain fibrils of amyloid-beta (Abeta) peptides, and synaptic AChE-S facilitates fibril formation by association with insoluble Abeta fibrils. Here, ... ...

    Abstract In Alzheimer's disease, both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) colocalize with brain fibrils of amyloid-beta (Abeta) peptides, and synaptic AChE-S facilitates fibril formation by association with insoluble Abeta fibrils. Here, we report that human BChE and BSP41, a synthetic peptide derived from the BChE C terminus, inversely associate with the soluble Abeta conformers and delay the onset and decrease the rate of Abeta fibril formation in vitro, at a 1:100 BChE/Abeta molar ratio and in a dose-dependent manner. The corresponding AChE synthetic peptide (ASP)40 peptide, derived from the homologous C terminus of synaptic human (h)AChE-S, failed to significantly affect Abeta fibril formation, attributing the role of enhancing this process to an AChE domain other than the C terminus. Circular dichroism and molecular modeling confirmed that both ASP40 and BChE synthetic peptide (BSP)41 are amphipathic alpha-helices. However, ASP40 shows symmetric amphipathicity, whereas BSP41 presented an aromatic tryptophan residue in the polar side of the C terminus. That this aromatic residue is causally involved in the attenuating effect of BChE was further supported by mutagenesis experiments in which (W8R) BSP41 showed suppressed capacity to attenuate fibril formation. In Alzheimer's disease, BChE may have thus acquired an inverse role to that of AChE by adopting imperfect amphipathic characteristics of its C terminus.
    MeSH term(s) Acetylcholinesterase/chemistry ; Amino Acid Sequence ; Amyloid/biosynthesis ; Amyloid/chemistry ; Amyloid/metabolism ; Butyrylcholinesterase/chemistry ; Butyrylcholinesterase/metabolism ; Conserved Sequence ; Humans ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Peptides/chemistry ; Solubility ; Structure-Activity Relationship
    Chemical Substances Amyloid ; Peptides ; Acetylcholinesterase (EC 3.1.1.7) ; Butyrylcholinesterase (EC 3.1.1.8)
    Language English
    Publishing date 2006-06-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.0602922103
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article: Acetylcholinesterase/C terminal binding protein interactions modify Ikaros functions, causing T lymphopenia.

    Perry, C / Pick, M / Podoly, E / Gilboa-Geffen, A / Zimmerman, G / Sklan, E H / Ben-Shaul, Y / Diamant, S / Soreq, H

    Leukemia

    2007  Volume 21, Issue 7, Page(s) 1472–1480

    Abstract: Hematological changes induced by various stress stimuli are accompanied by replacement of the primary acetylcholinesterase (AChE) 3' splice variant acetylcholinesterase-S (AChE-S) with the myelopoietic acetylcholinesterase-R (AChE-R) variant. To search ... ...

    Abstract Hematological changes induced by various stress stimuli are accompanied by replacement of the primary acetylcholinesterase (AChE) 3' splice variant acetylcholinesterase-S (AChE-S) with the myelopoietic acetylcholinesterase-R (AChE-R) variant. To search for putative acetylcholinesterase-S interactions with hematopoietic pathways, we employed a yeast two-hybrid screen. The transcriptional co-repressor C-terminal binding protein (CtBP) was identified as a protein partner of the AChE-S C terminus. In erythroleukemic K562 cells, AChE-S displayed nuclear colocalization and physical interaction with CtBP. Furthermore, co-transfected AChE-S reduced the co-repressive effect of CtBP over the hematopoietic transcription factor, Ikaros. In transgenic mice, overexpressed human (h) AChE-S mRNA induced selective bone marrow upregulation of Ikaros while suppressing FOG, another transcriptional partner of CtBP. Transgenic bone marrow cells showed a correspondingly elevated potential for producing progenitor colonies, compared with controls, while peripheral blood showed increased erythrocyte counts as opposed to reduced platelets, granulocytes and T lymphocytes. AChE's 3' alternative splicing, and the corresponding changes in AChE-S/CtBP interactions, thus emerge as being actively involved in controlling hematopoiesis and the potential for modulating immune functions, supporting reports on malfunctioning immune reactions under impaired splice site selection.
    MeSH term(s) Acetylcholinesterase/genetics ; Acetylcholinesterase/metabolism ; Acetylcholinesterase/physiology ; Alcohol Oxidoreductases/metabolism ; Alcohol Oxidoreductases/physiology ; Alternative Splicing/physiology ; Animals ; Bone Marrow Cells ; Cells, Cultured ; DNA-Binding Proteins/metabolism ; DNA-Binding Proteins/physiology ; Hematopoiesis/genetics ; Humans ; Ikaros Transcription Factor/physiology ; Isoenzymes/metabolism ; Isoenzymes/physiology ; Lymphopenia/etiology ; Mice ; Mice, Transgenic ; Protein Binding ; T-Lymphocytes
    Chemical Substances DNA-Binding Proteins ; IKZF1 protein, human ; Isoenzymes ; Ikaros Transcription Factor (148971-36-2) ; Alcohol Oxidoreductases (EC 1.1.-) ; C-terminal binding protein (EC 1.1.1.-) ; Acetylcholinesterase (EC 3.1.1.7)
    Language English
    Publishing date 2007-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/sj.leu.2404722
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2295: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article ; Online: The butyrylcholinesterase K variant confers structurally derived risks for Alzheimer pathology.

    Podoly, Erez / Shalev, Deborah E / Shenhar-Tsarfaty, Shani / Bennett, Estelle R / Ben Assayag, Einor / Wilgus, Harvey / Livnah, Oded / Soreq, Hermona

    The Journal of biological chemistry

    2009  Volume 284, Issue 25, Page(s) 17170–17179

    Abstract: The K variant of butyrylcholinesterase (BChE-K, 20% incidence) is a long debated risk factor for Alzheimer disease (AD). The A539T substitution in BChE-K is located at the C terminus, which is essential both for BChE tetramerization and for its capacity ... ...

    Abstract The K variant of butyrylcholinesterase (BChE-K, 20% incidence) is a long debated risk factor for Alzheimer disease (AD). The A539T substitution in BChE-K is located at the C terminus, which is essential both for BChE tetramerization and for its capacity to attenuate beta-amyloid (Abeta) fibril formation. Here, we report that BChE-K is inherently unstable as compared with the "usual" BChE (BChE-U), resulting in reduced hydrolytic activity and predicting prolonged acetylcholine maintenance and protection from AD. A synthetic peptide derived from the C terminus of BChE-K (BSP-K), which displayed impaired intermolecular interactions, was less potent in suppressing Abeta oligomerization than its BSP-U counterpart. Correspondingly, highly purified recombinant human rBChE-U monomers suppressed beta-amyloid fibril formation less effectively than dimers, which also protected cultured neuroblastoma cells from Abeta neurotoxicity. Dual activity structurally derived changes due to the A539T substitution can thus account for both neuroprotective characteristics caused by sustained acetylcholine levels and elevated AD risk due to inefficient interference with amyloidogenic processes.
    MeSH term(s) Aged ; Alzheimer Disease/enzymology ; Alzheimer Disease/etiology ; Alzheimer Disease/genetics ; Amino Acid Sequence ; Amino Acid Substitution ; Amyloid beta-Peptides/chemistry ; Amyloid beta-Peptides/metabolism ; Base Sequence ; Butyrylcholinesterase/chemistry ; Butyrylcholinesterase/genetics ; Butyrylcholinesterase/metabolism ; Cell Line ; DNA Primers/genetics ; Female ; Genetic Variation ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Neurons/metabolism ; Neuroprotective Agents/metabolism ; Polymorphism, Single Nucleotide ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Risk Factors
    Chemical Substances Amyloid beta-Peptides ; DNA Primers ; Neuroprotective Agents ; Recombinant Proteins ; Butyrylcholinesterase (EC 3.1.1.8)
    Language English
    Publishing date 2009-04-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M109.004952
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.108: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article ; Online: AChE and RACK1 promote the anti-inflammatory properties of fluoxetine.

    Waiskopf, Nir / Ofek, Keren / Gilboa-Geffen, Adi / Bekenstein, Uriya / Bahat, Assaf / Bennett, Estelle R / Podoly, Erez / Livnah, Oded / Hartmann, Gunther / Soreq, Hermona

    Journal of molecular neuroscience : MN

    2013  Volume 53, Issue 3, Page(s) 306–315

    Abstract: Selective serotonin reuptake inhibitors (SSRIs) show anti-inflammatory effects, suggesting a possible interaction with both Toll-like-receptor 4 (TLR4) responses and cholinergic signaling through as yet unclear molecular mechanism(s). Our results of ... ...

    Abstract Selective serotonin reuptake inhibitors (SSRIs) show anti-inflammatory effects, suggesting a possible interaction with both Toll-like-receptor 4 (TLR4) responses and cholinergic signaling through as yet unclear molecular mechanism(s). Our results of structural modeling support the concept that the antidepressant fluoxetine physically interacts with the TLR4-myeloid differentiation factor-2 complex at the same site as bacterial lipopolysaccharide (LPS). We also demonstrate reduced LPS-induced pro-inflammatory interleukin-6 and tumor necrosis factor alpha in human peripheral blood mononuclear cells preincubated with fluoxetine. Furthermore, we show that fluoxetine intercepts the LPS-induced decreases in intracellular acetylcholinesterase (AChE-S) and that AChE-S interacts with the nuclear factor kappa B (NFκB)-activating intracellular receptor for activated C kinase 1 (RACK1). This interaction may prevent NFκB activation by residual RACK1 and its interacting protein kinase PKCβII. Our findings attribute the anti-inflammatory properties of SSRI to surface membrane interference with leukocyte TLR4 activation accompanied by intracellular limitation of pathogen-inducible changes in AChE-S, RACK1, and PKCβII.
    MeSH term(s) Acetylcholinesterase/chemistry ; Acetylcholinesterase/metabolism ; Amino Acid Sequence ; Anti-Inflammatory Agents/pharmacology ; Binding Sites ; Fluoxetine/pharmacology ; GPI-Linked Proteins/chemistry ; GPI-Linked Proteins/metabolism ; GTP-Binding Proteins/chemistry ; GTP-Binding Proteins/metabolism ; Humans ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Lipopolysaccharides/pharmacology ; Molecular Docking Simulation ; Molecular Sequence Data ; Monocytes/drug effects ; Monocytes/metabolism ; Neoplasm Proteins/chemistry ; Neoplasm Proteins/metabolism ; Protein Binding ; Protein Kinase C beta/metabolism ; Receptors for Activated C Kinase ; Receptors, Cell Surface/chemistry ; Receptors, Cell Surface/metabolism ; Serotonin Uptake Inhibitors/pharmacology ; Toll-Like Receptor 4/chemistry ; Toll-Like Receptor 4/metabolism
    Chemical Substances Anti-Inflammatory Agents ; GPI-Linked Proteins ; Interleukin-6 ; Lipopolysaccharides ; Neoplasm Proteins ; RACK1 protein, human ; Receptors for Activated C Kinase ; Receptors, Cell Surface ; Serotonin Uptake Inhibitors ; TLR4 protein, human ; Toll-Like Receptor 4 ; Fluoxetine (01K63SUP8D) ; Protein Kinase C beta (EC 2.7.11.13) ; ACHE protein, human (EC 3.1.1.7) ; Acetylcholinesterase (EC 3.1.1.7) ; GTP-Binding Proteins (EC 3.6.1.-)
    Language English
    Publishing date 2013-11-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1043392-2
    ISSN 1559-1166 ; 0895-8696
    ISSN (online) 1559-1166
    ISSN 0895-8696
    DOI 10.1007/s12031-013-0174-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3006: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article: The Butyrylcholinesterase K Variant Confers Structurally Derived Risks for Alzheimer Pathology[diamond suit symbol]

    Podoly, Erez / Shalev, Deborah E / Shenhar-Tsarfaty, Shani / Bennett, Estelle R / Ben Assayag, Einor / Wilgus, Harvey / Livnah, Oded / Soreq, Hermona

    Journal of biological chemistry. 2009 June 19, v. 284, no. 25

    2009  

    Abstract: The K variant of butyrylcholinesterase (BChE-K, 20% incidence) is a long debated risk factor for Alzheimer disease (AD). The A539T substitution in BChE-K is located at the C terminus, which is essential both for BChE tetramerization and for its capacity ... ...

    Abstract The K variant of butyrylcholinesterase (BChE-K, 20% incidence) is a long debated risk factor for Alzheimer disease (AD). The A539T substitution in BChE-K is located at the C terminus, which is essential both for BChE tetramerization and for its capacity to attenuate β-amyloid (Aβ) fibril formation. Here, we report that BChE-K is inherently unstable as compared with the "usual" BChE (BChE-U), resulting in reduced hydrolytic activity and predicting prolonged acetylcholine maintenance and protection from AD. A synthetic peptide derived from the C terminus of BChE-K (BSP-K), which displayed impaired intermolecular interactions, was less potent in suppressing Aβ oligomerization than its BSP-U counterpart. Correspondingly, highly purified recombinant human rBChE-U monomers suppressed β-amyloid fibril formation less effectively than dimers, which also protected cultured neuroblastoma cells from Aβ neurotoxicity. Dual activity structurally derived changes due to the A539T substitution can thus account for both neuroprotective characteristics caused by sustained acetylcholine levels and elevated AD risk due to inefficient interference with amyloidogenic processes.
    Language English
    Dates of publication 2009-0619
    Size p. 17170-17179.
    Publishing place American Society for Biochemistry and Molecular Biology
    Document type Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Z 4' 65/118: Show issues
    Z 6.2: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top