Newly developed reversible MAO-B inhibitor circumvents the shortcomings of irreversible inhibitors in Alzheimer’s disease

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dc.contributor.authorPark J.-H.-
dc.contributor.authorJu Y.H.-
dc.contributor.authorChoi J.W.-
dc.contributor.authorSong H.J.-
dc.contributor.authorJang B.K.-
dc.contributor.authorWoo J.-
dc.contributor.authorChun H.-
dc.contributor.authorKim H.J.-
dc.contributor.authorShin S.J.-
dc.contributor.authorYarishkin O.-
dc.contributor.authorJo S.-
dc.contributor.authorPark M.-
dc.contributor.authorYeon S.K.-
dc.contributor.authorKim S.-
dc.contributor.authorKim J.-
dc.contributor.authorNam M.-H.-
dc.contributor.authorLondhe A.M.-
dc.contributor.authorKim J.-
dc.contributor.authorCho S.J.-
dc.contributor.authorCho S.-
dc.contributor.authorLee C.-
dc.contributor.authorHwang S.Y.-
dc.contributor.authorKim S.W.-
dc.contributor.authorOh S.-J.-
dc.contributor.authorCho J.-
dc.contributor.authorPae A.N.-
dc.contributor.authorJustin Lee C.-
dc.contributor.authorPark K.D.-
dc.date.available2019-07-19T05:38:45Z-
dc.date.created2019-04-23-
dc.date.issued2019-03-
dc.identifier.issn2375-2548-
dc.identifier.urihttps://pr.ibs.re.kr/handle/8788114/5886-
dc.description.abstractMonoamine oxidase–B (MAO-B) has recently emerged as a potential therapeutic target for Alzheimer’s disease (AD) because of its association with aberrant -aminobutyric acid (GABA) production in reactive astrocytes. Although short-term treatment with irreversible MAO-B inhibitors, such as selegiline, improves cognitive deficits in AD patients, long-term treatments have shown disappointing results. We show that prolonged treatment with selegiline fails to reduce aberrant astrocytic GABA levels and rescue memory impairment in APP/PS1 mice, an animal model of AD, because of increased activity in compensatory genes for a GABA-synthesizing enzyme, diamine oxidase (DAO). We have developed a potent, highly selective, and reversible MAO-B inhibitor, KDS2010 (IC 50 = 7.6 nM; 12,500-fold selectivity over MAO-A), which overcomes the disadvantages of the irreversible MAO-B inhibitor. Long-term treatment with KDS2010 does not induce compensatory mechanisms, thereby significantly attenuating increased astrocytic GABA levels and astrogliosis, enhancing synaptic transmission, and rescuing learning and memory impairments in APP/PS1 mice. Copyright © 2019 The Authors, some rights reserved-
dc.formatapplication/pdf-
dc.languageENG-
dc.publisherAMER ASSOC ADVANCEMENT SCIENCE-
dc.titleNewly developed reversible MAO-B inhibitor circumvents the shortcomings of irreversible inhibitors in Alzheimer’s disease-
dc.typeArticle-
dc.type.rimsA-
dc.identifier.wosid000462564300043-
dc.identifier.scopusid2-s2.0-85063344007-
dc.contributor.affiliatedAuthorJustin Lee C.-
dc.identifier.bibliographicCitationSCIENCE ADVANCES, v.5, no.3, pp.eaav0316 --
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > Journal Papers (저널논문)
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