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The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD

Monoamine oxidase (MAO) has been implicated in neuroinflammation, and therapies targeting MAO are of interest for neurodegenerative diseases. The small-molecule drug tranylcypromine, an inhibitor of MAO, is currently used as an antidepressant and in the treatment of cancer. However, whether tranylcy...

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Autores principales: Park, HyunHee, Han, Kyung-Min, Jeon, Hyongjun, Lee, Ji-Soo, Lee, Hyunju, Jeon, Seong Gak, Park, Jin-Hee, Kim, Yu Gyung, Lin, Yuxi, Lee, Young-Ho, Jeong, Yun Ha, Hoe, Hyang-Sook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563969/
https://www.ncbi.nlm.nih.gov/pubmed/32872335
http://dx.doi.org/10.3390/cells9091982
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author Park, HyunHee
Han, Kyung-Min
Jeon, Hyongjun
Lee, Ji-Soo
Lee, Hyunju
Jeon, Seong Gak
Park, Jin-Hee
Kim, Yu Gyung
Lin, Yuxi
Lee, Young-Ho
Jeong, Yun Ha
Hoe, Hyang-Sook
author_facet Park, HyunHee
Han, Kyung-Min
Jeon, Hyongjun
Lee, Ji-Soo
Lee, Hyunju
Jeon, Seong Gak
Park, Jin-Hee
Kim, Yu Gyung
Lin, Yuxi
Lee, Young-Ho
Jeong, Yun Ha
Hoe, Hyang-Sook
author_sort Park, HyunHee
collection PubMed
description Monoamine oxidase (MAO) has been implicated in neuroinflammation, and therapies targeting MAO are of interest for neurodegenerative diseases. The small-molecule drug tranylcypromine, an inhibitor of MAO, is currently used as an antidepressant and in the treatment of cancer. However, whether tranylcypromine can regulate LPS- and/or Aβ-induced neuroinflammation in the brain has not been well-studied. In the present study, we found that tranylcypromine selectively altered LPS-induced proinflammatory cytokine levels in BV2 microglial cells but not primary astrocytes. In addition, tranylcypromine modulated LPS-mediated TLR4/ERK/STAT3 signaling to alter neuroinflammatory responses in BV2 microglial cells. Importantly, tranylcypromine significantly reduced microglial activation as well as proinflammatory cytokine levels in LPS-injected wild-type mice. Moreover, injection of tranylcypromine in 5xFAD mice (a mouse model of AD) significantly decreased microglial activation but had smaller effects on astrocyte activation. Taken together, our results suggest that tranylcypromine can suppress LPS- and Aβ-induced neuroinflammatory responses in vitro and in vivo.
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spelling pubmed-75639692020-10-27 The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD Park, HyunHee Han, Kyung-Min Jeon, Hyongjun Lee, Ji-Soo Lee, Hyunju Jeon, Seong Gak Park, Jin-Hee Kim, Yu Gyung Lin, Yuxi Lee, Young-Ho Jeong, Yun Ha Hoe, Hyang-Sook Cells Article Monoamine oxidase (MAO) has been implicated in neuroinflammation, and therapies targeting MAO are of interest for neurodegenerative diseases. The small-molecule drug tranylcypromine, an inhibitor of MAO, is currently used as an antidepressant and in the treatment of cancer. However, whether tranylcypromine can regulate LPS- and/or Aβ-induced neuroinflammation in the brain has not been well-studied. In the present study, we found that tranylcypromine selectively altered LPS-induced proinflammatory cytokine levels in BV2 microglial cells but not primary astrocytes. In addition, tranylcypromine modulated LPS-mediated TLR4/ERK/STAT3 signaling to alter neuroinflammatory responses in BV2 microglial cells. Importantly, tranylcypromine significantly reduced microglial activation as well as proinflammatory cytokine levels in LPS-injected wild-type mice. Moreover, injection of tranylcypromine in 5xFAD mice (a mouse model of AD) significantly decreased microglial activation but had smaller effects on astrocyte activation. Taken together, our results suggest that tranylcypromine can suppress LPS- and Aβ-induced neuroinflammatory responses in vitro and in vivo. MDPI 2020-08-28 /pmc/articles/PMC7563969/ /pubmed/32872335 http://dx.doi.org/10.3390/cells9091982 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Park, HyunHee
Han, Kyung-Min
Jeon, Hyongjun
Lee, Ji-Soo
Lee, Hyunju
Jeon, Seong Gak
Park, Jin-Hee
Kim, Yu Gyung
Lin, Yuxi
Lee, Young-Ho
Jeong, Yun Ha
Hoe, Hyang-Sook
The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD
title The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD
title_full The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD
title_fullStr The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD
title_full_unstemmed The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD
title_short The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD
title_sort mao inhibitor tranylcypromine alters lps- and aβ-mediated neuroinflammatory responses in wild-type mice and a mouse model of ad
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563969/
https://www.ncbi.nlm.nih.gov/pubmed/32872335
http://dx.doi.org/10.3390/cells9091982
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