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@ARTICLE{Keller:151649,
      author       = {Keller, Sebastian and Polanski, Witold Henryk and
                      Enzensperger, Christoph and Reichmann, Heinz and Hermann,
                      Andreas and Gille, Gabriele},
      title        = {9-{M}ethyl-β-carboline inhibits monoamine oxidase activity
                      and stimulates the expression of neurotrophic factors by
                      astrocytes.},
      journal      = {Journal of neural transmission},
      volume       = {127},
      number       = {7},
      issn         = {1435-1463},
      address      = {Wien [u.a.]},
      publisher    = {Springer},
      reportid     = {DZNE-2020-01228},
      pages        = {999 - 1012},
      year         = {2020},
      abstract     = {β-Carbolines (BC) are pyridoindoles, which can be found in
                      various exogenous and endogenous sources. Recent studies
                      revealed neurostimulative, neuroprotective,
                      neuroregenerative and anti-inflammatory effects of
                      9-methyl-BC (9-Me-BC). Additionally, 9-me-BC increased
                      neurite outgrowth of dopaminergic neurons independent of
                      dopamine uptake into these neurons. In this study, the role
                      of astrocytes in neurostimulative, neuroregenerative and
                      neuroprotective properties of 9-me-BC was further
                      explored.9-Me-BC exerted anti-proliferative effects without
                      toxic properties in dopaminergic midbrain and cortical
                      astrocyte cultures. The organic cation transporter (OCT) but
                      not the dopamine transporter seem to mediate at least part
                      the effect of 9-me-BC on astrocytes. Remarkably, 9-me-BC
                      stimulated the gene expression of several important
                      neurotrophic factors for dopaminergic neurons like Artn,
                      Bdnf, Egln1, Tgfb2 and Ncam1. These factors are well known
                      to stimulate neurite outgrowth and to show neuroprotective
                      and neuroregenerative properties to dopaminergic neurons
                      against various toxins. Further, we show that effect of
                      9-me-BC is mediated through phosphatidylinositol 3-kinase
                      (PI3K) pathway. Additionally, 9-me-BC showed inhibitory
                      properties to monoamine oxidase (MAO) activity with an IC50
                      value of 1 µM for MAO-A and of 15.5 µM for MAO-B. The
                      inhibition of MAO by 9-me-BC might contribute to the
                      observed increased dopamine content and anti-apoptotic
                      properties in cell culture after 9-me-BC treatment in recent
                      studies. Thus, 9-me-BC have a plethora of beneficial effects
                      on dopaminergic neurons warranting its exploration as a new
                      multimodal anti-parkinsonian medication.},
      keywords     = {Animals / Astrocytes: drug effects / Astrocytes: enzymology
                      / Carbolines: pharmacology / Cells, Cultured / Dopaminergic
                      Neurons / Mice, Inbred C57BL / Monoamine Oxidase / Monoamine
                      Oxidase Inhibitors: pharmacology / Nerve Growth Factors:
                      metabolism / Phosphatidylinositol 3-Kinases},
      cin          = {AG Teipel},
      ddc          = {610},
      cid          = {I:(DE-2719)1510100},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC8592951},
      pubmed       = {pmid:32285253},
      doi          = {10.1007/s00702-020-02189-9},
      url          = {https://pub.dzne.de/record/151649},
}