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024 7 _ |a 10.1038/s41598-019-40887-x
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037 _ _ |a DZNE-2020-06895
041 _ _ |a English
082 _ _ |a 600
100 1 _ |a Cavaliere, Federica
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245 _ _ |a The tricyclic antidepressant clomipramine inhibits neuronal autophagic flux.
260 _ _ |a [London]
|c 2019
|b Macmillan Publishers Limited, part of Springer Nature
264 _ 1 |3 online
|2 Crossref
|b Springer Science and Business Media LLC
|c 2019-03-19
264 _ 1 |3 print
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|c 2019-12-01
336 7 _ |a article
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520 _ _ |a Antidepressants are commonly prescribed psychotropic substances for the symptomatic treatment of mood disorders. Their primary mechanism of action is the modulation of neurotransmission and the consequent accumulation of monoamines, such as serotonin and noradrenaline. However, antidepressants have additional molecular targets that, through multiple signaling cascades, may ultimately alter essential cellular processes. In this regard, it was previously demonstrated that clomipramine, a widely used FDA-approved tricyclic antidepressant, interferes with the autophagic flux and severely compromises the viability of tumorigenic cells upon cytotoxic stress. Consistent with this line of evidence, we report here that clomipramine undermines autophagosome formation and cargo degradation in primary dissociated neurons. A similar pattern was observed in the frontal cortex and liver of treated mice, as well as in the nematode Caenorhabditis elegans exposed to clomipramine. Together, our findings indicate that clomipramine may negatively regulate the autophagic flux in various tissues, with potential metabolic and functional implications for the homeostatic maintenance of differentiated cells.
536 _ _ |a 341 - Molecular Signaling (POF3-341)
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542 _ _ |i 2019-03-19
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650 _ 2 |a Affective Disorders, Psychotic: drug therapy
|2 MeSH
650 _ 2 |a Affective Disorders, Psychotic: pathology
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Antidepressive Agents, Tricyclic: adverse effects
|2 MeSH
650 _ 2 |a Antidepressive Agents, Tricyclic: pharmacology
|2 MeSH
650 _ 2 |a Autophagy: drug effects
|2 MeSH
650 _ 2 |a Caenorhabditis elegans: drug effects
|2 MeSH
650 _ 2 |a Clomipramine: adverse effects
|2 MeSH
650 _ 2 |a Clomipramine: pharmacology
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Liver: drug effects
|2 MeSH
650 _ 2 |a Liver: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Neurons: drug effects
|2 MeSH
650 _ 2 |a Neurons: metabolism
|2 MeSH
650 _ 2 |a Norepinephrine: metabolism
|2 MeSH
650 _ 2 |a Serotonin: metabolism
|2 MeSH
650 _ 2 |a Signal Transduction: drug effects
|2 MeSH
700 1 _ |a Fornarelli, Alessandra
|0 P:(DE-2719)2690858
|b 1
700 1 _ |a Bertan, Fabio
|0 P:(DE-2719)2810664
|b 2
700 1 _ |a Russo, Rossella
|b 3
700 1 _ |a Marsal Cots, Anais
|0 P:(DE-2719)2812207
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700 1 _ |a Morrone, Luigi Antonio
|b 5
700 1 _ |a Adornetto, Annagrazia
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700 1 _ |a Corasaniti, Maria Tiziana
|b 7
700 1 _ |a Bano, Daniele
|0 P:(DE-2719)2158358
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700 1 _ |a Bagetta, Giacinto
|b 9
700 1 _ |a Nicotera, Pierluigi
|0 P:(DE-2719)2010732
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773 1 8 |a 10.1038/s41598-019-40887-x
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773 _ _ |a 10.1038/s41598-019-40887-x
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856 4 _ |y OpenAccess
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856 7 _ |2 Pubmed Central
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Marc 21