Potential Roles of Myeloid Differentiation Factor 2 on Neuroinflammation and Its Possible Interventions
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Potential Roles of Myeloid Differentiation Factor 2 on Neuroinflammation and Its Possible Interventions Thura Tun Oo 1,2,3 & Wasana Pratchayasakul 1,2,3
&
Nipon Chattipakorn 1,2,3
&
Siriporn C. Chattipakorn 1,3,4
Received: 18 May 2020 / Accepted: 7 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Neuroinflammation . Myeloid differentiation factor 2 . Toll-like receptor 4 . Lipopolysaccharide . Brain function
Introduction Neuroinflammation has been generally defined as an inflammatory response of central nervous system (CNS) following a variety of endogenous and exogenous insults such as trauma, pathogens, tissue damage, stress, seizures, autoimmune diseases, and/or neurodegenerative diseases [1–6]. This inflammation is a complex CNS defense mechanism, resulting in a protective immune response and tissue repair. Cellular and molecular immune components, including microglia and astrocytes, cytokines, complement, and pattern-recognition receptors (PRRs), are the key players in the process of
* Siriporn C. Chattipakorn [email protected]; [email protected] 1
Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
2
Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
3
Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, Thailand
4
Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
neuroinflammation [7]. The activation of microglia and astrocytes in response to internal or external stimuli contributes to neuronal injury and brain damage [8]. In addition, previous studies have demonstrated that prolonged neuroinflammation could lead to neurodegenerative diseases, such as Alzheimer’s disease (AD) [9–13]. Ther
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