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  1. Book ; Online: Molecular Psychiatry

    Rein, Theo / Fries, Gabriel R.

    2020  

    Keywords Medicine ; Mental health services ; cardiovascular disease ; cell adhesion molecules ; immunology ; inflammation ; nervous system ; schizophrenia ; bipolar disorder ; major depressive disorder ; DNA methylation ; response variability ; antipsychotics ; drug design ; multi-target drugs ; polypharmacology ; multi-task learning ; machine learning ; biomarker discovery ; psychiatry ; serotonin ; 5-HT 4 receptor ; 5-HT4R ; depression ; mood disorder ; expression ; Alzheimer's disease ; cognition ; Parkinson's disease ; forced swimming ; Roman rat lines ; stress ; hippocampus ; BDNF ; trkB ; PSA-NCAM ; western blot ; immunohistochemistry ; general cognitive function ; intelligence ; GWAS ; genetic correlation ; childhood-onset schizophrenia (COS) ; induced pluripotent stem cell (iPSC) ; copy number variation (CNV) ; early neurodevelopment ; neuronal differentiation ; synapse ; dendritic arborization ; miRNAs ; stress physiology ; cytoskeleton ; actin dynamics ; DRR1 ; TU3A ; FAM107A ; acid sphingomyelinase ; alcohol dependence ; liver enzymes ; sphingolipid metabolism ; withdrawal ; Hsp90 ; GR ; stress response ; steroid hormones ; molecular chaperones ; psychiatric disease ; circadian rhythms ; FKBP51 ; FKBP52 ; CyP40 ; PP5 ; DISC1 ; neurodevelopment ; CRMP-2 ; proteomics ; antidepressant treatment ; HPA axis ; gene expression ; FKBP5 ; sleep ; sleep EEG ; biomarkers ; antidepressants ; cordance ; gender ; sex difference ; antidepressant ; rapid-acting ; Ketamine ; endocrinology ; electroconvulsive therapy ; basic-helix-loop-helix ; brain ; coactivator ; glucocorticoids ; mineralocorticoid receptor knockout ; transcription biology ; dopaminergic gene polymorphisms ; affective temperament ; obesity ; alpha-synuclein ; SNCA ; major depression ; Hamilton Scale of Depression ; chemokines ; neuroinflammation ; social defeat ; Immune response ; T cells ; susceptibility ; resilience ; Treg cells ; Th17 cells ; behavior ; PPARγ ; n/a
    Size 1 electronic resource (288 pages)
    Publisher MDPI - Multidisciplinary Digital Publishing Institute
    Publishing place Basel, Switzerland
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT021044565
    ISBN 9783039361212 ; 303936121X
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article: FKBP5-Liganden: potenzielle Antidepressiva und mehr? FKBP51-Inhibitoren

    Rein, Theo

    Psychopharmakotherapie

    2022  Volume 29, Issue 3, Page(s) 78

    Language German
    Document type Article
    ZDB-ID 1196510-1
    ISSN 0944-6877
    Database Current Contents Medicine

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4299: Show issues Location:
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  3. Article ; Online: Harnessing autophagy to fight SARS-CoV-2: An update in view of recent drug development efforts.

    Rein, Theo

    Journal of cellular biochemistry

    2021  Volume 123, Issue 2, Page(s) 155–160

    Abstract: Drug repurposing is an attractive option for identifying new treatment strategies, in particular in extraordinary situations of urgent need such as the current coronavirus disease 2019 (Covid-19) pandemic. Recently, the World Health Organization ... ...

    Abstract Drug repurposing is an attractive option for identifying new treatment strategies, in particular in extraordinary situations of urgent need such as the current coronavirus disease 2019 (Covid-19) pandemic. Recently, the World Health Organization announced testing of three drugs as potential Covid-19 therapeutics that are known for their dampening effect on the immune system. Thus, the underlying concept of selecting these drugs is to temper the potentially life-threatening overshooting of the immune system reacting to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This viewpoint discusses the possibility that the impact of these and other drugs on autophagy contributes to their therapeutic effect by hampering the SARS-CoV-2 life cycle.
    MeSH term(s) Antidepressive Agents/pharmacology ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Artesunate/pharmacology ; Artesunate/therapeutic use ; Autophagy/drug effects ; COVID-19/drug therapy ; Chloroquine/pharmacology ; Drug Development ; Drug Repositioning ; Endoplasmic Reticulum/drug effects ; Endoplasmic Reticulum/physiology ; Endoplasmic Reticulum/virology ; Endosomes/drug effects ; Endosomes/virology ; Humans ; Hydroxychloroquine/pharmacology ; Imatinib Mesylate/pharmacology ; Imatinib Mesylate/therapeutic use ; Infliximab/pharmacology ; Infliximab/therapeutic use ; Intracellular Membranes/drug effects ; Intracellular Membranes/physiology ; Intracellular Membranes/virology ; Ivermectin/pharmacology ; Macrolides/pharmacology ; Middle East Respiratory Syndrome Coronavirus/drug effects ; Niclosamide/pharmacology ; Niclosamide/therapeutic use ; Pandemics ; RNA, Viral/metabolism ; SARS-CoV-2/drug effects ; SARS-CoV-2/physiology ; Virus Replication
    Chemical Substances Antidepressive Agents ; Antiviral Agents ; Macrolides ; RNA, Viral ; bafilomycin A (116764-51-3) ; Hydroxychloroquine (4QWG6N8QKH) ; Artesunate (60W3249T9M) ; Ivermectin (70288-86-7) ; Chloroquine (886U3H6UFF) ; Imatinib Mesylate (8A1O1M485B) ; Niclosamide (8KK8CQ2K8G) ; Infliximab (B72HH48FLU)
    Language English
    Publishing date 2021-10-20
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 392402-6
    ISSN 1097-4644 ; 0730-2312
    ISSN (online) 1097-4644
    ISSN 0730-2312
    DOI 10.1002/jcb.30166
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1114: Show issues Location:
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  4. Article ; Online: Peptidylprolylisomerases, Protein Folders, or Scaffolders? The Example of FKBP51 and FKBP52.

    Rein, Theo

    BioEssays : news and reviews in molecular, cellular and developmental biology

    2020  Volume 42, Issue 7, Page(s) e1900250

    Abstract: Peptidylprolyl-isomerases (PPIases) comprise of the protein families of FK506 binding proteins (FKBPs), cyclophilins, and parvulins. Their common feature is their ability to expedite the transition of peptidylprolyl bonds between the cis and the trans ... ...

    Abstract Peptidylprolyl-isomerases (PPIases) comprise of the protein families of FK506 binding proteins (FKBPs), cyclophilins, and parvulins. Their common feature is their ability to expedite the transition of peptidylprolyl bonds between the cis and the trans conformation. Thus, it seemed highly plausible that PPIase enzymatic activity is crucial for protein folding. However, this has been difficult to prove over the decades since their discovery. In parallel, more and more studies have discovered scaffolding functions of PPIases. This essay discusses the hypothesis that PPIase enzymatic activity might be the consequence of binding to peptidylprolyl protein motifs. The main focus of this paper is the large immunophilins FKBP51 and FKBP52, but other PPIases such as cyclophilin A and Pin1 are also described. From the hypothesis, it follows that the PPIase activity of these proteins might be less relevant, if at all, than the organization of protein complexes through versatile protein binding. Also see the video abstract here https://youtu.be/A33la0dx5LE.
    MeSH term(s) Cyclophilins ; Protein Binding ; Protein Folding ; Tacrolimus Binding Proteins
    Chemical Substances Cyclophilins (EC 5.2.1.-) ; Tacrolimus Binding Proteins (EC 5.2.1.-) ; tacrolimus binding protein 4 (EC 5.2.1.-)
    Language English
    Publishing date 2020-04-22
    Publishing country United States
    Document type Journal Article ; Video-Audio Media
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.201900250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2024: Show issues Location:
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  5. Article ; Online: Post-translational modifications and stress adaptation: the paradigm of FKBP51.

    Rein, Theo

    Biochemical Society transactions

    2020  Volume 48, Issue 2, Page(s) 441–449

    Abstract: Adaptation to stress is a fundamental requirement to cope with changing environmental conditions that pose a threat to the homeostasis of cells and organisms. Post-translational modifications (PTMs) of proteins represent a possibility to quickly produce ... ...

    Abstract Adaptation to stress is a fundamental requirement to cope with changing environmental conditions that pose a threat to the homeostasis of cells and organisms. Post-translational modifications (PTMs) of proteins represent a possibility to quickly produce proteins with new features demanding relatively little cellular resources. FK506 binding protein (FKBP) 51 is a pivotal stress protein that is involved in the regulation of several executers of PTMs. This mini-review discusses the role of FKBP51 in the function of proteins responsible for setting the phosphorylation, ubiquitination and lipidation of other proteins. Examples include the kinases Akt1, CDK5 and GSK3β, the phosphatases calcineurin, PP2A and PHLPP, and the ubiquitin E3-ligase SKP2. The impact of FKBP51 on PTMs of signal transduction proteins significantly extends the functional versatility of this protein. As a stress-induced protein, FKBP51 uses re-setting of PTMs to relay the effect of stress on various signaling pathways.
    MeSH term(s) Cyclin-Dependent Kinase 5/metabolism ; Glycogen Synthase Kinase 3 beta/metabolism ; Humans ; Lipids/chemistry ; Nuclear Proteins/metabolism ; Phosphoprotein Phosphatases/metabolism ; Phosphorylation ; Protein Binding ; Protein Phosphatase 2/metabolism ; Protein Processing, Post-Translational ; Proto-Oncogene Proteins c-akt/metabolism ; S-Phase Kinase-Associated Proteins/metabolism ; Signal Transduction ; Stress, Physiological ; Tacrolimus Binding Proteins/metabolism ; Ubiquitin/chemistry
    Chemical Substances Lipids ; Nuclear Proteins ; S-Phase Kinase-Associated Proteins ; SKP2 protein, human ; Ubiquitin ; AKT1 protein, human (EC 2.7.11.1) ; Cyclin-Dependent Kinase 5 (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; CDK5 protein, human (EC 2.7.11.22) ; PHLPP1 protein, human (EC 3.1.3.16) ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; Protein Phosphatase 2 (EC 3.1.3.16) ; Tacrolimus Binding Proteins (EC 5.2.1.-) ; tacrolimus binding protein 5 (EC 5.2.1.8)
    Keywords covid19
    Language English
    Publishing date 2020-04-21
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 184237-7
    ISSN 1470-8752 ; 0300-5127
    ISSN (online) 1470-8752
    ISSN 0300-5127
    DOI 10.1042/BST20190332
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 944: Show issues Location:
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  6. Article: Is Autophagy Involved in the Diverse Effects of Antidepressants?

    Rein, Theo

    Cells

    2019  Volume 8, Issue 1

    Abstract: Autophagy has received increased attention as a conserved process governing cellular energy and protein homeostasis that is thus relevant in a range of physiological and pathophysiological conditions. Recently, autophagy has also been linked to ... ...

    Abstract Autophagy has received increased attention as a conserved process governing cellular energy and protein homeostasis that is thus relevant in a range of physiological and pathophysiological conditions. Recently, autophagy has also been linked to depression, mainly through its involvement in the action of antidepressants. Some antidepressant drugs and psychotropic medication have been reported to exert beneficial effects in other diseases, for example, in cancer and neurodegenerative diseases. This review collates the evidence for the hypothesis that autophagy contributes to the effects of antidepressants beyond depression treatment.
    MeSH term(s) Aging/drug effects ; Animals ; Antidepressive Agents/adverse effects ; Antidepressive Agents/therapeutic use ; Autophagy/drug effects ; Communicable Diseases/drug therapy ; Depression/drug therapy ; Disease Models, Animal ; Humans ; Inflammation/drug therapy ; Neoplasms/drug therapy ; Neurodegenerative Diseases/drug therapy
    Chemical Substances Antidepressive Agents
    Language English
    Publishing date 2019-01-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells8010044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Is Autophagy Involved in the Diverse Effects of Antidepressants?

    Theo Rein

    Cells, Vol 8, Iss 1, p

    2019  Volume 44

    Abstract: Autophagy has received increased attention as a conserved process governing cellular energy and protein homeostasis that is thus relevant in a range of physiological and pathophysiological conditions. Recently, autophagy has also been linked to ... ...

    Abstract Autophagy has received increased attention as a conserved process governing cellular energy and protein homeostasis that is thus relevant in a range of physiological and pathophysiological conditions. Recently, autophagy has also been linked to depression, mainly through its involvement in the action of antidepressants. Some antidepressant drugs and psychotropic medication have been reported to exert beneficial effects in other diseases, for example, in cancer and neurodegenerative diseases. This review collates the evidence for the hypothesis that autophagy contributes to the effects of antidepressants beyond depression treatment.
    Keywords autophagy ; antidepressants ; depression ; cancer ; FKBP51 ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Peptidylprolylisomerases, Protein Folders, or Scaffolders? The Example of FKBP51 and FKBP52

    Rein, Theo

    BioEssays. 2020 July, v. 42, no. 7

    2020  

    Abstract: Peptidylprolyl‐isomerases (PPIases) comprise of the protein families of FK506 binding proteins (FKBPs), cyclophilins, and parvulins. Their common feature is their ability to expedite the transition of peptidylprolyl bonds between the cis and the trans ... ...

    Abstract Peptidylprolyl‐isomerases (PPIases) comprise of the protein families of FK506 binding proteins (FKBPs), cyclophilins, and parvulins. Their common feature is their ability to expedite the transition of peptidylprolyl bonds between the cis and the trans conformation. Thus, it seemed highly plausible that PPIase enzymatic activity is crucial for protein folding. However, this has been difficult to prove over the decades since their discovery. In parallel, more and more studies have discovered scaffolding functions of PPIases. This essay discusses the hypothesis that PPIase enzymatic activity might be the consequence of binding to peptidylprolyl protein motifs. The main focus of this paper is the large immunophilins FKBP51 and FKBP52, but other PPIases such as cyclophilin A and Pin1 are also described. From the hypothesis, it follows that the PPIase activity of these proteins might be less relevant, if at all, than the organization of protein complexes through versatile protein binding. Also see the video abstract here https://youtu.be/A33la0dx5LE.
    Keywords cyclophilin A ; enzyme activity ; peptidylprolyl isomerase
    Language English
    Dates of publication 2020-07
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note NAL-AP-2-clean ; JOURNAL ARTICLE
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.201900250
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

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  9. Article: SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection

    Niemeyer, Daniela / Corman, Victor Max / ZANNAS, ANTHONY / Herrmann, Alexander / Drosten, Christian / Mueller, Marcel / Rein, Theo

    Nature Communications, 10:5770

    2019  

    Abstract: Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly- ... ...

    Institution Charité - Universitätsmedizin Berlin
    Max-Planck-Institut für Psychiatrie (München)
    Helmholtz Zentrum München
    Deutsches Zentrum für Infektionsforschung
    Abstract Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions.
    Keywords COVID-19 ; Coronavirus ; Antivirals ; MERS-CoV ; Macroautophagy ; Middle East respiratory syndrome coronavirus ; Ubiquitin ligases
    Language English
    Document type Article
    Database Repository for Life Sciences

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  10. Article ; Online: Effects of the nerve agent VX on hiPSC-derived motor neurons.

    Schaefers, Catherine / Schmeißer, Wolfgang / John, Harald / Worek, Franz / Rein, Theo / Rothmiller, Simone / Schmidt, Annette

    Archives of toxicology

    2024  

    Abstract: Poisoning with the organophosphorus nerve agent VX can be life-threatening due to limitations of the standard therapy with atropine and oximes. To date, the underlying pathomechanism of VX affecting the neuromuscular junction has not been fully ... ...

    Abstract Poisoning with the organophosphorus nerve agent VX can be life-threatening due to limitations of the standard therapy with atropine and oximes. To date, the underlying pathomechanism of VX affecting the neuromuscular junction has not been fully elucidated structurally. Results of recent studies investigating the effects of VX were obtained from cells of animal origin or immortalized cell lines limiting their translation to humans. To overcome this limitation, motor neurons (MN) of this study were differentiated from in-house feeder- and integration-free-derived human-induced pluripotent stem cells (hiPSC) by application of standardized and antibiotic-free differentiation media with the aim to mimic human embryogenesis as closely as possible. For testing VX sensitivity, MN were initially exposed once to 400 µM, 600 µM, 800 µM, or 1000 µM VX and cultured for 5 days followed by analysis of changes in viability and neurite outgrowth as well as at the gene and protein level using µLC-ESI MS/HR MS, XTT, IncuCyte, qRT-PCR, and Western Blot. For the first time, VX was shown to trigger neuronal cell death and decline in neurite outgrowth in hiPSC-derived MN in a time- and concentration-dependent manner involving the activation of the intrinsic as well as the extrinsic pathway of apoptosis. Consistent with this, MN morphology and neurite network were altered time and concentration-dependently. Thus, MN represent a valuable tool for further investigation of the pathomechanism after VX exposure. These findings might set the course for the development of a promising human neuromuscular test model and patient-specific therapies in the future.
    Language English
    Publishing date 2024-03-30
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 124992-7
    ISSN 1432-0738 ; 0340-5761
    ISSN (online) 1432-0738
    ISSN 0340-5761
    DOI 10.1007/s00204-024-03708-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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