Home > Publications Database > 9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes. > print

001     151649
005     20240322115502.0
024 7 _ |a pmc:PMC8592951
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024 7 _ |a 10.1007/s00702-020-02189-9
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024 7 _ |a pmid:32285253
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024 7 _ |a 0300-9564
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024 7 _ |a 1435-1463
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024 7 _ |a 0375-9245
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024 7 _ |a 0022-3026
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037 _ _ |a DZNE-2020-01228
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Keller, Sebastian
|b 0
245 _ _ |a 9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes.
260 _ _ |a Wien [u.a.]
|c 2020
|b Springer
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520 _ _ |a 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.
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650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Astrocytes: drug effects
|2 MeSH
650 _ 2 |a Astrocytes: enzymology
|2 MeSH
650 _ 2 |a Carbolines: pharmacology
|2 MeSH
650 _ 2 |a Cells, Cultured
|2 MeSH
650 _ 2 |a Dopaminergic Neurons
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Monoamine Oxidase
|2 MeSH
650 _ 2 |a Monoamine Oxidase Inhibitors: pharmacology
|2 MeSH
650 _ 2 |a Nerve Growth Factors: metabolism
|2 MeSH
650 _ 2 |a Phosphatidylinositol 3-Kinases
|2 MeSH
700 1 _ |a Polanski, Witold Henryk
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700 1 _ |a Enzensperger, Christoph
|b 2
700 1 _ |a Reichmann, Heinz
|b 3
700 1 _ |a Hermann, Andreas
|0 P:(DE-2719)2811732
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|u dzne
700 1 _ |a Gille, Gabriele
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773 _ _ |a 10.1007/s00702-020-02189-9
|g Vol. 127, no. 7, p. 999 - 1012
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|t Journal of neural transmission
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|y 2020
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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