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  1. Article: Is There a Role of Autophagy in Depression and Antidepressant Action?

    Gassen, Nils C / Rein, Theo

    Frontiers in psychiatry

    2019  Volume 10, Page(s) 337

    Abstract: Autophagy has been recognized as evolutionary conserved intracellular pathway that ensures energy, organelle, and protein homeostasis through lysosomal degradation of damaged macromolecules and organelles. It is activated under various stress situations, ...

    Abstract Autophagy has been recognized as evolutionary conserved intracellular pathway that ensures energy, organelle, and protein homeostasis through lysosomal degradation of damaged macromolecules and organelles. It is activated under various stress situations, e.g., food deprivation or proteotoxic conditions. Autophagy has been linked to several diseases, more recently also including stress-related diseases such as depression. A growing number of publications report on the role of autophagy in neurons, also referred to as "neuronal autophagy" on the one hand, and several studies describe effects of antidepressants-or of compounds that exert antidepressant-like actions-on autophagy on the other hand. This minireview highlights the emerging evidence for the involvement of autophagy in the pathology and treatment of depression and discusses current limitations as well as potential avenues for future research.
    Language English
    Publishing date 2019-05-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564218-2
    ISSN 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2019.00337
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: FKBP5/FKBP51 on weight watch: central FKBP5 links regulatory WIPI protein networks to autophagy and metabolic control.

    Bajaj, Thomas / Häusl, Alexander S / Schmidt, Mathias V / Gassen, Nils C

    Autophagy

    2022  Volume 18, Issue 11, Page(s) 2756–2758

    Abstract: Stress and changes in energy stores are perceived by hormone- and nutrient-sensing nuclei of the hypothalamus, which orchestrate an adaptive physiological body response to maintain homeostasis. Macroautophagy/autophagy is a fundamental lysosomal ... ...

    Abstract Stress and changes in energy stores are perceived by hormone- and nutrient-sensing nuclei of the hypothalamus, which orchestrate an adaptive physiological body response to maintain homeostasis. Macroautophagy/autophagy is a fundamental lysosomal degradation system contributing to preservation of proteome balance and metabolic homeostasis. Its dysregulation is linked to diverse human pathologies, including neuropsychiatric and metabolic disorders. Autophagy is coordinated by cellular nutrient sensors, including AMPK and MTORC1 that interact with WIPI proteins. Studies suggest that WDR45/WIPI4 interacts with the stress-sensitive co-chaperone FKBP5/FKBP51, which has emerged as a key autophagy scaffold. However, the impact of FKBP5 on autophagy signaling in response to metabolic challenges, such as a high-fat diet, is elusive. Therefore, we manipulated FKBP5 in the mediobasal hypothalamus (MBH) and studied autophagy signaling and protein interactions in their physiological context. We identified FKBP5 as a scaffold of the STK11/LKB1-AMPK complex with WDR45/WIPI4 and TSC2 with WDR45B/WIPI3 in response to metabolic challenges, positioning FKBP5 in major nutrient-sensing and autophagy-regulating networks. Intriguingly, we could demonstrate that
    MeSH term(s) AMP-Activated Protein Kinases/metabolism ; Autophagy/physiology ; Carrier Proteins ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Obesity/genetics ; Animals ; Mice ; Tacrolimus Binding Proteins/genetics
    Chemical Substances AMP-Activated Protein Kinases (EC 2.7.11.31) ; Carrier Proteins ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; tacrolimus binding protein 5 (EC 5.2.1.8) ; Tacrolimus Binding Proteins (EC 5.2.1.-)
    Language English
    Publishing date 2022-04-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2022.2063006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Hippo Signaling: Emerging Pathway in Stress-Related Psychiatric Disorders?

    Stepan, Jens / Anderzhanova, Elmira / Gassen, Nils C

    Frontiers in psychiatry

    2018  Volume 9, Page(s) 715

    Abstract: Discovery of the Hippo pathway and its core components has made a significant impact on our progress in the understanding of organ development, tissue homeostasis, and regeneration. Upon diverse extracellular and intracellular stimuli, Hippo signaling ... ...

    Abstract Discovery of the Hippo pathway and its core components has made a significant impact on our progress in the understanding of organ development, tissue homeostasis, and regeneration. Upon diverse extracellular and intracellular stimuli, Hippo signaling regulates stemness, cell proliferation and apoptosis by a well-conserved signaling cascade, and disruption of these systems has been implicated in cancer as well as metabolic and neurodegenerative diseases. The central role of Hippo signaling in cell biology also results in prominent links to stress-regulated pathways. Genetic variations, epigenetically provoked upregulation of Hippo pathway members and dysregulation of cellular processes implicated in learning and memory, are linked to an increased risk of stress-related psychiatric disorders (SRPDs). In this review, we summarize recent findings, supporting the role of Hippo signaling in SRPDs by canonical and non-canonical Hippo pathway interactions.
    Language English
    Publishing date 2018-12-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564218-2
    ISSN 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2018.00715
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: The Role of Cathepsins in Memory Functions and the Pathophysiology of Psychiatric Disorders.

    Niemeyer, Christine / Matosin, Natalie / Kaul, Dominic / Philipsen, Alexandra / Gassen, Nils C

    Frontiers in psychiatry

    2020  Volume 11, Page(s) 718

    Abstract: Cathepsins are proteases with functions in cellular homeostasis, lysosomal degradation and autophagy. Their role in the development of neurodegenerative diseases has been extensively studied. It is well established that impairment of proper cathepsin ... ...

    Abstract Cathepsins are proteases with functions in cellular homeostasis, lysosomal degradation and autophagy. Their role in the development of neurodegenerative diseases has been extensively studied. It is well established that impairment of proper cathepsin function plays a crucial role in the pathophysiology of neurodegenerative diseases, and in recent years a role for cathepsins in mental disorders has emerged given the involvement of cathepsins in memory function, hyperactivity, and in depression- and anxiety-like behavior. Here we review putative cathepsin functions with a special focus on their role in the pathophysiology of psychiatric diseases. Specifically, cathepsins are crucial for maintaining cellular homeostasis, particularly as part of the autophagy machinery of neural strategies underlying acute stress response. Disruption of cathepsin functions can lead to psychiatric diseases such as major depressive disease (MDD), bipolar disorder, and schizophrenia. Specifically, cathepsins can be excreted
    Language English
    Publishing date 2020-07-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564218-2
    ISSN 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2020.00718
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Focus on FKBP51: A molecular link between stress and metabolic disorders.

    Häusl, Alexander S / Balsevich, Georgia / Gassen, Nils C / Schmidt, Mathias V

    Molecular metabolism

    2019  Volume 29, Page(s) 170–181

    Abstract: Background: Obesity, Type 2 diabetes (T2D) as well as stress-related disorders are rising public health threats and major burdens for modern society. Chronic stress and depression are highly associated with symptoms of the metabolic syndrome, but the ... ...

    Abstract Background: Obesity, Type 2 diabetes (T2D) as well as stress-related disorders are rising public health threats and major burdens for modern society. Chronic stress and depression are highly associated with symptoms of the metabolic syndrome, but the molecular link is still not fully understood. Furthermore, therapies tackling these biological disorders are still lacking. The identification of shared molecular targets underlying both pathophysiologies may lead to the development of new treatments. The FK506 binding protein 51 (FKBP51) has recently been identified as a promising therapeutic target for stress-related psychiatric disorders and obesity-related metabolic outcomes.
    Scope of the review: The aim of this review is to summarize current evidence of in vitro, preclinical, and human studies on the stress responsive protein FKBP51, focusing on its newly discovered role in metabolism. Also, we highlight the therapeutic potential of FKBP51 as a new treatment target for symptoms of the metabolic syndrome.
    Major conclusions: We conclude the review by emphasizing missing knowledge gaps that remain and future research opportunities needed to implement FKBP51 as a drug target for stress-related obesity or T2D.
    MeSH term(s) Adipogenesis ; Animals ; Energy Metabolism ; Glucose/metabolism ; Humans ; Metabolic Diseases/metabolism ; Metabolic Diseases/pathology ; Obesity/metabolism ; Obesity/pathology ; Stress, Psychological ; Tacrolimus Binding Proteins/genetics ; Tacrolimus Binding Proteins/metabolism
    Chemical Substances Tacrolimus Binding Proteins (EC 5.2.1.-) ; tacrolimus binding protein 5 (EC 5.2.1.8) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2019-09-11
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2708735-9
    ISSN 2212-8778 ; 2212-8778
    ISSN (online) 2212-8778
    ISSN 2212-8778
    DOI 10.1016/j.molmet.2019.09.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A genetic variant of fatty acid amide hydrolase (FAAH) exacerbates hormone-mediated orexigenic feeding in mice.

    Balsevich, Georgia / Petrie, Gavin N / Heinz, Daniel E / Singh, Arashdeep / Aukema, Robert J / Hunker, Avery C / Vecchiarelli, Haley A / Yau, Hiulan / Sticht, Martin / Thompson, Roger J / Lee, Francis S / Zweifel, Larry S / Chelikani, Prasanth K / Gassen, Nils C / Hill, Matthew N

    eLife

    2023  Volume 12

    Abstract: Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide. A polymorphism ... ...

    Abstract Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide. A polymorphism in
    MeSH term(s) Mice ; Humans ; Animals ; Agouti-Related Protein ; AMP-Activated Protein Kinases ; Endocannabinoids/metabolism ; Amidohydrolases/metabolism ; Obesity
    Chemical Substances anandamide (UR5G69TJKH) ; fatty-acid amide hydrolase (EC 3.5.1.-) ; Agouti-Related Protein ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Endocannabinoids ; Amidohydrolases (EC 3.5.-)
    Language English
    Publishing date 2023-04-11
    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.81919
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The emerging role of FKBP5 in the regulation of metabolism and body weight.

    Zannas, Anthony S / Balsevich, Georgia / Gassen, Nils C

    Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery

    2016  Volume 12, Issue 8, Page(s) 1560–1561

    MeSH term(s) Humans ; Obesity, Morbid ; Polymorphism, Single Nucleotide
    Language English
    Publishing date 2016-09
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2274243-8
    ISSN 1878-7533 ; 1550-7289
    ISSN (online) 1878-7533
    ISSN 1550-7289
    DOI 10.1016/j.soard.2016.05.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: The FKBP51 Glucocorticoid Receptor Co-Chaperone: Regulation, Function, and Implications in Health and Disease.

    Fries, Gabriel R / Gassen, Nils C / Rein, Theo

    International journal of molecular sciences

    2017  Volume 18, Issue 12

    Abstract: Among the chaperones and co-chaperones regulating the glucocorticoid receptor (GR), FK506 binding protein (FKBP) 51 is the most intensely investigated across different disciplines. This review provides an update on the role of the different co-chaperones ...

    Abstract Among the chaperones and co-chaperones regulating the glucocorticoid receptor (GR), FK506 binding protein (FKBP) 51 is the most intensely investigated across different disciplines. This review provides an update on the role of the different co-chaperones of Hsp70 and Hsp90 in the regulation of GR function. The development leading to the focus on FKBP51 is outlined. Further, a survey of the vast literature on the mechanism and function of FKBP51 is provided. This includes its structure and biochemical function, its regulation on different levels-transcription, post-transcription, and post-translation-and its function in signaling pathways. The evidence portraying FKBP51 as a scaffolding protein organizing protein complexes rather than a chaperone contributing to the folding of individual proteins is collated. Finally, FKBP51's involvement in physiology and disease is outlined, and the promising efforts in developing drugs targeting FKBP51 are discussed.
    MeSH term(s) Animals ; Humans ; Receptors, Glucocorticoid/genetics ; Receptors, Glucocorticoid/metabolism ; Tacrolimus Binding Proteins/genetics ; Tacrolimus Binding Proteins/metabolism
    Chemical Substances Receptors, Glucocorticoid ; Tacrolimus Binding Proteins (EC 5.2.1.-) ; tacrolimus binding protein 5 (EC 5.2.1.8)
    Language English
    Publishing date 2017-12-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms18122614
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Tricyclic antidepressants target FKBP51 SUMOylation to restore glucocorticoid receptor activity.

    Budziñski, Maia L / Sokn, Clara / Gobbini, Romina / Ugo, Belén / Antunica-Noguerol, María / Senin, Sergio / Bajaj, Thomas / Gassen, Nils C / Rein, Theo / Schmidt, Mathias V / Binder, Elisabeth B / Arzt, Eduardo / Liberman, Ana C

    Molecular psychiatry

    2022  Volume 27, Issue 5, Page(s) 2533–2545

    Abstract: FKBP51 is an important inhibitor of the glucocorticoid receptor (GR) signaling. High FKBP51 levels are associated to stress-related disorders, which are linked to GR resistance. SUMO conjugation to FKBP51 is necessary for FKBP51's inhibitory action on GR. ...

    Abstract FKBP51 is an important inhibitor of the glucocorticoid receptor (GR) signaling. High FKBP51 levels are associated to stress-related disorders, which are linked to GR resistance. SUMO conjugation to FKBP51 is necessary for FKBP51's inhibitory action on GR. The GR/FKBP51 pathway is target of antidepressant action. Thus we investigated if these drugs could inhibit FKBP51 SUMOylation and therefore restore GR activity. Screening cells using Ni
    MeSH term(s) Animals ; Antidepressive Agents, Tricyclic/pharmacology ; Clomipramine ; Gene Expression Regulation ; Mice ; Rats ; Receptors, Glucocorticoid/metabolism ; Sumoylation ; Tacrolimus Binding Proteins/metabolism
    Chemical Substances Antidepressive Agents, Tricyclic ; Receptors, Glucocorticoid ; Tacrolimus Binding Proteins (EC 5.2.1.-) ; Clomipramine (NUV44L116D)
    Language English
    Publishing date 2022-03-08
    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/s41380-022-01491-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: The FKBP51 Glucocorticoid Receptor Co-Chaperone

    Gabriel R. Fries / Nils C. Gassen / Theo Rein

    International Journal of Molecular Sciences, Vol 18, Iss 12, p

    Regulation, Function, and Implications in Health and Disease

    2017  Volume 2614

    Abstract: Among the chaperones and co-chaperones regulating the glucocorticoid receptor (GR), FK506 binding protein (FKBP) 51 is the most intensely investigated across different disciplines. This review provides an update on the role of the different co-chaperones ...

    Abstract Among the chaperones and co-chaperones regulating the glucocorticoid receptor (GR), FK506 binding protein (FKBP) 51 is the most intensely investigated across different disciplines. This review provides an update on the role of the different co-chaperones of Hsp70 and Hsp90 in the regulation of GR function. The development leading to the focus on FKBP51 is outlined. Further, a survey of the vast literature on the mechanism and function of FKBP51 is provided. This includes its structure and biochemical function, its regulation on different levels—transcription, post-transcription, and post-translation—and its function in signaling pathways. The evidence portraying FKBP51 as a scaffolding protein organizing protein complexes rather than a chaperone contributing to the folding of individual proteins is collated. Finally, FKBP51’s involvement in physiology and disease is outlined, and the promising efforts in developing drugs targeting FKBP51 are discussed.
    Keywords chaperone ; glucocorticoid receptor ; FKBP51 ; FKBP5 ; signaling pathway ; drug ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 570
    Language English
    Publishing date 2017-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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