, Volume 20, Issue 3, pp 151–158 | Cite as

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

  • Kyoungho Suk
  • Jiyeon Ock
Inflammation in acute and chronic neurological and psychiatric diseases


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.


Chemical genetics Microglia Neuroinflammation Neuroprotection Neurodegenerative diseases Obovatol Synthetic compounds 



Central nervous system


Nitric oxide




Reactive oxygen species


Tumor necrosis factor alpha


Interleukin 1 beta


Inducible nitric-oxide synthase


Mitogen-activated protein kinase


Extracellular signal-regulated kinases


c-Jun N-terminal kinase


Nuclear factor kappa B


Isolectin B4


Monocyte chemoattractant protein 1


Macrophage inflammatory protein 1 alpha


Liquid chromatography–mass spectrometry/mass spectrometry


Peroxiredoxin 2



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).

Conflicts of interest

None to declare related to this study.


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Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Department of Pharmacology, Brain Science and Engineering Institute, CMRIKyungpook National University School of MedicineDaeguKorea

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