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  Paroxetine binding and activation of phosphofructokinase implicates energy metabolism in antidepressant mode of action

Park, D. I., Novak, B., Yan, Y., Kaya, M. E., & Turck, C. W. (2020). Paroxetine binding and activation of phosphofructokinase implicates energy metabolism in antidepressant mode of action. JOURNAL OF PSYCHIATRIC RESEARCH, 129, 8-14. doi:10.1016/j.jpsychires.2020.05.033.

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Datensatz-Permalink: https://hdl.handle.net/21.11116/0000-0008-A86B-3 Versions-Permalink: https://hdl.handle.net/21.11116/0000-0008-D3CD-3
Genre: Zeitschriftenartikel

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 Urheber:
Park, Dong Ik1, Autor           
Novak, Bozidar1, Autor           
Yan, Yu2, Autor           
Kaya, Melahat Ezgi1, Autor           
Turck, Christoph W.2, Autor           
Affiliations:
1Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035295              
2RG Proteomics and Biomarkers, Max Planck Institute of Psychiatry, Max Planck Society, ou_2040287              

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Schlagwörter: NITRIC-OXIDE SYNTHASE; MICE; 6-PHOSPHOFRUCTO-1-KINASE; STRESSPsychiatry; Cellular thermal shift assay; Target engagement; Selective serotonin reuptake inhibitor; Phosphofructokinase;
 Zusammenfassung: Selective serotonin reuptake inhibitors (SSRIs) are the predominant drugs prescribed for Major Depressive Disorder. The immediate pharmacological target of SSRIs is the serotonin transporter. However, the delayed therapeutic effect and high rate of patient non-response make it highly likely that SSRIs also have other molecular targets that are yet to be identified. Cellular thermal shift assay (CETSA) is a method based on thermal stabilization of target proteins upon drug binding. In the present study, we show that the SSRI paroxetine binds to phosphofructokinase (PFK) protein using CETSA. We found that mouse brain PFK and recombinant human PFK proteins are stabilized by paroxetine incubation. Chronic paroxetine treatment also significantly increased mouse brain PFK thermal stability. Paroxetine significantly elevated in vitro and in vivo PFK activity. Levels of several metabolites in glutamate- and energy metabolism-related pathways are significantly correlated with PFK activity in mouse hippocampus. Our data show that paroxetine can bind to PFK and affect its activity. Implications of these results for the antidepressant mode of action of paroxetine are discussed.

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Sprache(n): eng - English
 Datum: 2020
 Publikationsstatus: Erschienen
 Seiten: 7
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: ISI: 000571186500002
DOI: 10.1016/j.jpsychires.2020.05.033
 Art des Abschluß: -

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Titel: JOURNAL OF PSYCHIATRIC RESEARCH
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND : PERGAMON-ELSEVIER SCIENCE LTD
Seiten: - Band / Heft: 129 Artikelnummer: - Start- / Endseite: 8 - 14 Identifikator: ISSN: 0022-3956