9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Sebastian Keller - , TUD Dresden University of Technology (Author)
  • Witold Henryk Polanski - , Department of Neurology, Department of Neurosurgery, TUD Dresden University of Technology (Author)
  • Christoph Enzensperger - , Friedrich Schiller University Jena, SmartDyeLivery GmbH (Author)
  • Heinz Reichmann - , Department of Neurology, TUD Dresden University of Technology (Author)
  • Andreas Hermann - , TUD Dresden University of Technology, University of Rostock, German Center for Neurodegenerative Diseases (DZNE) (Author)
  • Gabriele Gille - , TUD Dresden University of Technology (Author)

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.

Details

Original languageEnglish
Pages (from-to)999-1012
Number of pages14
JournalJournal of Neural Transmission
Volume127
Issue number7
Publication statusPublished - 1 Jul 2020
Peer-reviewedYes

External IDs

PubMed 32285253
ORCID /0000-0002-6603-5375/work/148606651

Keywords

Sustainable Development Goals

Keywords

  • 9-Methyl-β-carboline, Astrocytes, Dopaminergic neurons, Inhibition of monoamine oxidase A and B, Neurotrophic factors