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Chemical genetics of neuroinflammation: natural and synthetic compounds as microglial inhibitors

  • Inflammation in acute and chronic neurological and psychiatric diseases
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Abstract

Chemical genetics is a new field of study that employs diverse small-molecule compounds to interrogate specific biological functions. The chemical genetics approach has been recently applied to microglial biology. Microglial cells are the primary immune cells of the brain, and are believed to play a major role in both host defense and tissue repair in the central nervous system. However, excessive microglial activation with overexpression of proinflammatory cytokines and oxidative stress products is linked to the progression of several neurodegenerative diseases. Therefore, suppression of microglial activation and subsequent neuroinflammation may be a potential therapeutic approach against these diseases. From microglia cell-based assays, the natural compound obovatol and several synthetic compounds were identified as inhibitors of microglial activation. They showed strong anti-neuroinflammatory activities in various in vitro and in vivo studies. Nuclear factor-κB and mitogen-activated protein kinase pathways were found to be related to the effects of these compounds on microglia. In particular, based on the affinity purification approach, peroxiredoxin 2 was identified as a microglial target of obovatol. Thus, natural and synthetic compounds are not only important biological tools for the study of microglial physiology and pathology, but they are also attractive candidates for the development of therapeutic drugs against neuroinflammatory and neurodegenerative diseases.

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Abbreviations

CNS:

Central nervous system

NO:

Nitric oxide

LPS:

Lipopolysaccharide

ROS:

Reactive oxygen species

TNF-α:

Tumor necrosis factor alpha

IL-1β:

Interleukin 1 beta

iNOS:

Inducible nitric-oxide synthase

MAPK:

Mitogen-activated protein kinase

ERK:

Extracellular signal-regulated kinases

JNK:

c-Jun N-terminal kinase

NF-κB:

Nuclear factor kappa B

IB4:

Isolectin B4

MCP-1:

Monocyte chemoattractant protein 1

MIP-1α:

Macrophage inflammatory protein 1 alpha

LC–MS/MS:

Liquid chromatography–mass spectrometry/mass spectrometry

Prx2:

Peroxiredoxin 2

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Acknowledgments

The authors’ laboratory was supported by the National Research Foundation (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) of Korean government (No. 2009-0078941). This work was also supported by Basic Science Research Program through the NRF funded by the MEST (No. 2010-0029460).

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None to declare related to this study.

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Authors and Affiliations

  1. Department of Pharmacology, Brain Science and Engineering Institute, CMRI, Kyungpook National University School of Medicine, 680 Gukchaebosang Street, Joong-gu, Daegu, 700-422, Korea

    Kyoungho Suk & Jiyeon Ock

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  1. Kyoungho Suk
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  2. Jiyeon Ock
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Correspondence to Kyoungho Suk.

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Suk, K., Ock, J. Chemical genetics of neuroinflammation: natural and synthetic compounds as microglial inhibitors. Inflammopharmacol 20, 151–158 (2012). https://doi.org/10.1007/s10787-011-0108-2

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  • DOI: https://doi.org/10.1007/s10787-011-0108-2

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