Monoamine oxidases in development

Wang, Chi Chiu; Billett, E. Ellen; Borchert, Astrid; Kühn, Hartmut; Ufer, Christoph

doi:10.1007/s00018-012-1065-7

Cited by 58 publications

(26 citation statements)

References 259 publications

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“…Studies have shown that MAO-B levels increase during aging 38,39 and MAO-A upregulation in the heart causes oxidative mitochondrial damage. 40 GSH-Px was able to depose the peroxide, forming water and oxygen and, as a result, protect against oxidative injury.…”

Section: Effects Of Ofe and Acteoside On Aging-related Factorsmentioning

confidence: 99%

Osmanthus fragrans Flower Extract and Acteoside Protect Against d-Galactose-Induced Aging in an ICR Mouse Model

Xiong

Mao

et al. 2016

Journal of Medicinal Food

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Osmanthus fragrans flower extract (OFE) is an organic extract from O. fragrans flower, which exhibits neuroprotective, free radical scavenging, and antioxidant effects. Therefore, the protective effect of OFE and acteoside against aging was studied. An aging ICR mouse model was established by chronically administering d-galactose (250 mg/kg) for 8 weeks. d-galactose induced spatial learning and memory impairments that were successfully inhibited by OFE and acteoside, which could shorten escape latency, improve platform crossing times, and increase zone time. The antioxidant potential of OFE and acteoside in vivo was evaluated by estimating the following: activities of antioxidant enzymes, such as glutathione peroxidase and aging-related enzyme, particularly monoamine oxidase; contents of lipid peroxidation methane dicarboxylic aldehyde, advanced glycation end products, and 8-hydroxy-2'-deoxyguanosine (a DNA damage product); and levels of nuclear factor-erythroid 2-related factor 2. OFE and acteoside also inhibited d-galactose-induced neurological aging by suppressing the increase in glial fibrillary acidic protein and neurotrophin-3. Considering the dose-dependent protective effects of OFE and acteoside, we concluded that OFE, rich in acteoside, was a good source of natural antiaging compounds.

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Section: Effects Of Ofe and Acteoside On Aging-related Factorsmentioning

confidence: 99%

Osmanthus fragrans Flower Extract and Acteoside Protect Against d-Galactose-Induced Aging in an ICR Mouse Model

Xiong

Mao

et al. 2016

Journal of Medicinal Food

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“…In humans MAO A is predominantly found in adrenergic, catecholaminergic and dopaminergic neurons and deactivates serotonin, dopamine, norepinephrine and epinephrine. Human MAO B participates in dopamine degradation and is mainly expressed in serotonergic neurons and glial cells1415. Therefore, MAO inhibitors are frequently investigated for treatment of depression and Parkinson’s disease16.…”

mentioning

confidence: 99%

Ciproxifan, a histamine H3 receptor antagonist, reversibly inhibits monoamine oxidase A and B

Hagenow

Stasiak

Ramsay

et al. 2017

Sci Rep

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Ciproxifan is a well-investigated histamine H3 receptor (H3R) inverse agonist/antagonist, showing an exclusively high species-specific affinity at rodent compared to human H3R. It is well studied as reference compound for H3R in rodent models for neurological diseases connected with neurotransmitter dysregulation, e.g. attention deficit hyperactivity disorder or Alzheimer’s disease. In a screening for potential monoamine oxidase A and B inhibition ciproxifan showed efficacy on both enzyme isoforms. Further characterization of ciproxifan revealed IC50 values in a micromolar concentration range for human and rat monoamine oxidases with slight preference for monoamine oxidase B in both species. The inhibition by ciproxifan was reversible for both human isoforms. Regarding inhibitory potency of ciproxifan on rat brain MAO, these findings should be considered, when using high doses in rat models for neurological diseases. As the H3R and monoamine oxidases are all capable of affecting neurotransmitter modulation in brain, we consider dual targeting ligands as interesting approach for treatment of neurological disorders. Since ciproxifan shows only moderate activity at human targets, further investigations in animals are not of primary interest. On the other hand, it may serve as starting point for the development of dual targeting ligands.

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Die Therapie von komplexen neurodegenerativen Erkrankungen erfordert eine Entwicklung von Multitargetorientierten Wirkstoffen. [6] Dies führt zum einen zur Verminderung der katalytischen Oxidation von biogenen Aminen, wie Serotonin (5-HT), Norepinephrin und Dopamin, die an kognitiven Prozessen beteiligt sind, und zum anderen zur verminderten Erzeugung von ROS, die zum neuronalen Zelltod führen kçnnen. Diese zeigten ein ausbalanciertes Wirkprofil an den gewünschten Targets in zumeist nanomolaren Konzentrationsbereichen.

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Multipotente Liganden mit kombinierter Cholinesterase‐ und Monoaminooxidase‐Inhibition sowie Histamin‐H₃R‐Antagonismus bei neurodegenerativen Erkrankungen

et al. 2017

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Die Therapie von komplexen neurodegenerativen Erkrankungen erfordert eine Entwicklung von Multitargetorientierten Wirkstoffen. Durchs trukturelle Optimierung des neuroprotektiven Liganden ASS234 mittels Integration etablierter Pharmakophore des Histamin-H 3 -Rezeptors (H3R) konnten neuartige Indolderivate mit inhibitorischer Aktivität an Acetylcholin-/Butyrylcholinesterasen und Monoaminooxidasen Aund BsowieamH3R erzielt werden. Diese zeigten ein ausbalanciertes Wirkprofil an den gewünschten Targets in zumeist nanomolaren Konzentrationsbereichen. Weiterführende In-vitro-Untersuchungen zeigten antioxidative und neuroprotektive Fähigkeiten sowie die Überwindung der Blut-Hirn-Schranke.M it diesem vielversprechenden Wirkprofil zeigte Contilisant (bei 1mgkg À1 i.p.) eine signifikante Verbesserung von Lipopolysaccharid-induzierten kognitiven Defiziten. Morbus Alzheimer und Morbus Parkinson zählen zu den häufigsten neurodegenerativen Erkrankungen, welche durch komplexe und vielfältige Mechanismen gekennzeichnet sind. Bei der Suche nach mçglichen Krankheitsursachen sowie effizienteren Therapieoptionen stellten sich mitochondriale Dysfunktionen, Neuroinflammation und oxidativer Stress als Schlüsselfaktoren bei der Entstehung und dem Fortschreiten dieser Erkrankungen heraus.Folglich ist die Entwicklung von antioxidativen Wirkstoffstrategien fürd iese Erkrankungen, insbesondere fürM orbus Alzheimer,v on großer Bedeutung. [1,2] Der kürzlich beschriebene Multitarget-orientierten Ligand (MTL) ASS234 (Abbildung 1) [3][4][5] zeigt eine irreversible Hemmung der Monoaminooxidasen Aund B(MAOA/ B) und reduziert die Entstehung des Sekundärproduktes Wasserstoffperoxid, eine reaktive Sauerstoffspezies (ROS). [6] Dies führt zum einen zur Verminderung der katalytischen Oxidation von biogenen Aminen, wie Serotonin (5-HT), Norepinephrin und Dopamin, die an kognitiven Prozessen beteiligt sind, und zum anderen zur verminderten Erzeugung von ROS, die zum neuronalen Zelltod führen kçnnen. ASS234 zeigt zusätzlich eine reversible Inhibition von Ace-[*] S. Hagenow, [+] J.

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Monoamine oxidases in development

Cited by 58 publications

References 259 publications

Osmanthus fragrans Flower Extract and Acteoside Protect Against d-Galactose-Induced Aging in an ICR Mouse Model

Osmanthus fragrans Flower Extract and Acteoside Protect Against d-Galactose-Induced Aging in an ICR Mouse Model

Ciproxifan, a histamine H3 receptor antagonist, reversibly inhibits monoamine oxidase A and B

Multipotente Liganden mit kombinierter Cholinesterase‐ und Monoaminooxidase‐Inhibition sowie Histamin‐H₃R‐Antagonismus bei neurodegenerativen Erkrankungen

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Monoamine oxidases in development

Cited by 58 publications

References 259 publications

Osmanthus fragrans Flower Extract and Acteoside Protect Against d-Galactose-Induced Aging in an ICR Mouse Model

Osmanthus fragrans Flower Extract and Acteoside Protect Against d-Galactose-Induced Aging in an ICR Mouse Model

Ciproxifan, a histamine H3 receptor antagonist, reversibly inhibits monoamine oxidase A and B

Multipotente Liganden mit kombinierter Cholinesterase‐ und Monoaminooxidase‐Inhibition sowie Histamin‐H3R‐Antagonismus bei neurodegenerativen Erkrankungen

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Product

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Multipotente Liganden mit kombinierter Cholinesterase‐ und Monoaminooxidase‐Inhibition sowie Histamin‐H₃R‐Antagonismus bei neurodegenerativen Erkrankungen