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Potential Roles of Myeloid Differentiation Factor 2 on Neuroinflammation and Its Possible Interventions

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Abstract

Neuroinflammation is the primary response by immune cells in the nervous system to protect against infection. Chronic and uncontrolled neuroinflammation triggers neuronal injury and neuronal death resulting in a variety of neurodegenerative disorders. Therefore, fine tuning of the immune response in the nervous system is now extensively considered as a potential therapeutic intervention for those diseases. The immune cells of the nervous system express Toll-like receptor 4 (TLR4) together with myeloid differentiation factor 2 (MD-2) to protect against the pathogens. Over the last 10 years, antagonists targeting the functional domains of MD-2 have become attractive pharmacological intervention strategies in pre-clinical studies into neuroinflammation and its associated brain pathologies. This review aims to summarize and discuss the roles of TLR4-MD-2 signaling pathway activation in various models of neuroinflammation. This review article also highlights the studies reporting the effect of MD-2 antagonists on neuroinflammation in in vitro and in vivo studies.

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Funding

This work was supported by the Senior Research Scholar grant from the National Research Council of Thailand (SCC), the Thailand Science Research and Innovation grant DBG6280006 (NC), and RSA6180071 (WP), the NSTDA Research Chair grant from the National Science and Technology Development Agency Thailand (NC), and the Chiang Mai University Center of Excellence Award (NC).

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  1. Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

    Thura Tun Oo, Wasana Pratchayasakul, Nipon Chattipakorn & Siriporn C. Chattipakorn

  2. Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

    Thura Tun Oo, Wasana Pratchayasakul & Nipon Chattipakorn

  3. Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, Thailand

    Thura Tun Oo, Wasana Pratchayasakul, Nipon Chattipakorn & Siriporn C. Chattipakorn

  4. Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

    Siriporn C. Chattipakorn

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Oo, T.T., Pratchayasakul, W., Chattipakorn, N. et al. Potential Roles of Myeloid Differentiation Factor 2 on Neuroinflammation and Its Possible Interventions. Mol Neurobiol 57, 4825–4844 (2020). https://doi.org/10.1007/s12035-020-02066-2

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