The exceptional properties of 9‐methyl‐β‐carboline: stimulation, protection and regeneration of dopaminergic neurons coupled with anti‐inflammatory effects

Polanski, Witold H; Enzensperger, Christoph; Reichmann, Heinz; Gille, Gabriele

doi:10.1111/j.1471-4159.2010.06725.x

Cited by 31 publications

(65 citation statements)

References 69 publications

(145 reference statements)

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“…for a period of 10 days improved spatial learning and stimulated synthesis of DA in hippocampus. It could increase DA, dendritic length/complexity and the number of dendritic spines in hippocampal formation [47,27,48]. Furthermore, it has been shown that 9-me-BC had protective and regenerative/restorative effects on dopaminergic neurons by inducing the gene expression of several neurotrophic factors and dow-regulating apoptotic cell signals.…”

Section: Discussionmentioning

confidence: 99%

Low and high doses of Norharmane respectively improve and impair learning and memory in streptozotocin-induced rat model of sporadic alzheimer’s disease

Hossein¹,

Charmchi²,

Behnaz³

2017

Alzheimers Dement Cogn Neurol

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Section: Discussionmentioning

confidence: 99%

Low and high doses of Norharmane respectively improve and impair learning and memory in streptozotocin-induced rat model of sporadic alzheimer’s disease

Hossein¹,

Charmchi²,

Behnaz³

2017

Alzheimers Dement Cogn Neurol

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“…9-Me-BC exerted neurostimulatory, neuroprotective, neuroregenerative and anti-inflammatory effects in primary dopaminergic culture [22,61]. While toxic effects of 9-methylated b-carbolines were reported in former in vivo studies with mice [62], recent research has confirmed the neuroprotective properties of 9-me-BC in a rat model [63].…”

Section: Review Polanski Reichmann and Gillementioning

confidence: 98%

“…After treatment of primary dopaminergic cell cultures with 9-me-BC for 48 h, an increased number of tyrosine hydroxylase immunoreactive (THir) neurons were observed [22]. This concentration-dependent effect reached its peak at 90 µM when 30% more THir neurons were counted.…”

Section: Reviewmentioning

confidence: 99%

“…BCs, especially methylated forms such as 2,9-dimethyl-b-carbolinium ion (2,9-dime-BC + ), have been shown to exert neurotoxic effects on dopaminergic neurons [20]. They decreased dopamine uptake, induced apoptosis via increased caspase 3 levels, inhibited mitochondrial complex I, enhanced formation of ROS and activated glia and microglia [21][22][23][24]. Furthermore, harman and norharman inhibited the topoisomerase in cell nuclei and thus disturbed the DNA repair after UV-or chemical-induced DNA damage [25].…”

Section: Review Polanski Reichmann and Gillementioning

confidence: 99%

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Stimulation, protection and regeneration of dopaminergic neurons by 9-methyl-β-carboline: a new anti-Parkinson drug?

Polanski

Reichmann

Gille

2011

Expert Review of Neurotherapeutics

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β-carbolines are potential endogenous and exogenous neurotoxins that may contribute to the pathogenesis of Parkinson's disease (PD). 9-methyl-β-carboline exhibits multimodal effects that could be beneficial in the treatment of PD. It shows stimulatory effects to dopaminergic neurons by increasing the expression of tyrosine hydroxylase and its transcription factors in pre-existing dopa decarboxylase immunoreactive neurons. Furthermore, 9-methyl-β-carboline has emerged as a substance with the rare property of a protective and regenerative/restorative potential for dopaminergic neurons by inducing gene expression of several neurotrophic factors and decreasing apoptotic cell signals. It reduces protein levels of α-synuclein and inhibits monoamine oxidase A and B. Finally, 9-methyl-β-carboline acts on multiple targets in the inflammatory cascade by inhibiting the proliferation of microglia, by decreasing chemotactic cytokines and by creating an anti-inflammatory environment in the CNS. This article summarizes our current knowledge of 9-methyl-carboline and discusses its potential role as a new drug for the treatment of PD.

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“…Lastly, also similar to isoquinolines, not all beta-carbolines are neurotoxic as there are a few studies showing the neuroprotective effects both in vitro and in vivo of 9-methyl-beta-carboline such as protection against rotenone-or MPP+-induced neurodegeneration, reduced activation of microglia and its pro-inflammatory response and reduction of alpha-synuclein level (Polanski et al, 2010;Wernicke et al, 2010). …”

Section: Beta-carbolinesmentioning

confidence: 99%

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

Choi¹,

Polcher²,

Joas³

2016

EFSA Supporting Publications

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This report presents the outcomes of a systematic review (SR) identifying the mechanisms and chemicals involved in the pathogenesis of Parkinson's disease (PD) and childhood leukaemia (CL). This work serves as a basis for defining and mapping the causal linkages between a molecular initiating event (MIE) and a final adverse outcome (AO) that are relevant for the development of a prototype adverse outcome pathway (AOP) for assessing risk factors for PD and CL. Search for literature from 1990 to present was conducted using Web of Science, PubMed and TOXNET, and relevant references were selected using established inclusion/exclusion criteria and ranked using a set of quality control factors.For PD, 7,384 individual references were identified to be relevant for PD pathogenesis and chemicals associated with PD. Dopaminergic neurodegeneration in the substantia nigra leading to locomotor deficits was identified as the AO in PD. Other identified key events in PD pathogenesis include mitochondrial dysfunction, cellular accumulation of alpha-synuclein and oxidative stress. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone and paraquat are some chemicals identified to be associated with PD pathogenesis.For CL, 1,988 individual references were identified to be relevant for CL pathogenesis and chemicals associated with CL. Chromosomal translocation, genetic damage/mutation and hyperdiploidy are considered as driving forces of CL. Except for infant leukaemia, CL pathogenesis requires a 'two-hit' model with an initiating event occurring in utero followed by a secondary hit potentially occurring after birth. Potential MIEs leading to these driving mechanisms include aberrant DNA topoisomerase II activity and erroneous DNA repair. Epigenetics appears to also play an influential role in CL pathogenesis. Benzene, bioflavonoids and organophosphates are some chemicals identified to be implicated in CL pathogenesis.The challenges of developing AOPs for these two diseases and the data gaps identified from the outcomes of this SR are also elaborated in this report. The present document has been produced and adopted by the bodies identified above as authors. This task has been carried out exclusively by the authors in the context of a contract between the European Food Safety Authority and the authors, awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. KEY WORDSSystematic Review, Parkinson Disease, Childhood Leukaemia, Pathogenesis, Chemicals, Pesticides, Adverse Outcome Pathway SUMMARYThe aim of this project was to perform a systematic review (SR) to collect relevant publications related to the mechanisms involved in the pathogenesis of Parkinson's disease (PD)...

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The exceptional properties of 9‐methyl‐β‐carboline: stimulation, protection and regeneration of dopaminergic neurons coupled with anti‐inflammatory effects

Cited by 31 publications

References 69 publications

Low and high doses of Norharmane respectively improve and impair learning and memory in streptozotocin-induced rat model of sporadic alzheimer’s disease

Low and high doses of Norharmane respectively improve and impair learning and memory in streptozotocin-induced rat model of sporadic alzheimer’s disease

Stimulation, protection and regeneration of dopaminergic neurons by 9-methyl-β-carboline: a new anti-Parkinson drug?

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

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