首页    期刊浏览 2024年11月25日 星期一
登录注册

文章基本信息

  • 标题:The tricyclic antidepressant clomipramine inhibits neuronal autophagic flux
  • 本地全文:下载
  • 作者:Federica Cavaliere ; Alessandra Fornarelli ; Fabio Bertan
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2019
  • 卷号:9
  • 期号:1
  • 页码:1-9
  • DOI:10.1038/s41598-019-40887-x
  • 出版社:Springer Nature
  • 摘要: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.
国家哲学社会科学文献中心版权所有