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

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

  • Cells. 2020 Aug 28;9(9):1982. doi: 10.3390/cells9091982.
HyunHee Park 1,  Kyung-Min Han 1 2,  Hyongjun Jeon 1,  Ji-Soo Lee 1,  Hyunju Lee 1,  Seong Gak Jeon 1,  Jin-Hee Park 1,  Yu Gyung Kim 1 3,  Yuxi Lin 4,  Young-Ho Lee 4 5 6,  Yun Ha Jeong 1,  Hyang-Sook Hoe 1 2
Affiliations

Affiliations

  • 1 Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, Korea.
  • 2 Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology, Daegu 42988, Korea.
  • 3 Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Korea.
  • 4 Research Center of Bioconvergence Analysis, Korea Basic Science Institute (KBSI), Ochang, Cheongju, Chungbuk 28119, Korea.
  • 5 Neurovascular Research Group, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, Korea.
  • 6 Bio-Analytical Science, University of Science and Technology (UST), Gajeong-ro, Yuseong-gu, Daejeon 34113, Korea.
PMID: 32872335 DOI: 10.3390/cells9091982
Abstract

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.

Keywords

LPS; MAO inhibitor; amyloid beta; microglia; neuroinflammation.

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