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      Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes

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          Abstract

          Neuroinflammation is associated with neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Microglia and astrocytes are key regulators of inflammatory responses in the central nervous system. The activation of microglia and astrocytes is heterogeneous and traditionally categorized as neurotoxic (M1-phenotype microglia and A1-phenotype astrocytes) or neuroprotective (M2-phenotype microglia and A2-phenotype astrocytes). However, this dichotomized classification may not reflect the various phenotypes of microglia and astrocytes. The relationship between these activated glial cells is also very complicated, and the phenotypic distribution can change, based on the progression of neurodegenerative diseases. A better understanding of the roles of microglia and astrocytes in neurodegenerative diseases is essential for developing effective therapies. In this review, we discuss the roles of inflammatory response in neurodegenerative diseases, focusing on the contributions of microglia and astrocytes and their relationship. In addition, we discuss biomarkers to measure neuroinflammation and studies on therapeutic drugs that can modulate neuroinflammation.

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          Neurotoxic reactive astrocytes are induced by activated microglia

          A reactive astrocyte subtype termed A1 is induced after injury or disease of the central nervous system and subsequently promotes the death of neurons and oligodendrocytes.
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            Neuroinflammation in Alzheimer's disease.

            Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.
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              Macrophage plasticity and polarization: in vivo veritas.

              Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to IFNs, Toll-like receptor engagement, or IL-4/IL-13 signaling, macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a universe of activation states. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1-M2 or M2-like polarized activation. Functional skewing of mononuclear phagocytes occurs in vivo under physiological conditions (e.g., ontogenesis and pregnancy) and in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer). However, in selected preclinical and clinical conditions, coexistence of cells in different activation states and unique or mixed phenotypes have been observed, a reflection of dynamic changes and complex tissue-derived signals. The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for macrophage-centered diagnostic and therapeutic strategies.
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                Author and article information

                Contributors
                ksh213@hanyang.ac.kr
                Journal
                Transl Neurodegener
                Transl Neurodegener
                Translational Neurodegeneration
                BioMed Central (London )
                2047-9158
                26 November 2020
                26 November 2020
                2020
                : 9
                : 42
                Affiliations
                [1 ]GRID grid.49606.3d, ISNI 0000 0001 1364 9317, Department of Neurology, , Hanyang University College of Medicine, ; Seoul, Republic of Korea
                [2 ]GRID grid.49606.3d, ISNI 0000 0001 1364 9317, Department of Translational Medicine, , Hanyang University Graduate School of Biomedical Science & Engineering, ; Seoul, Republic of Korea
                Author information
                http://orcid.org/0000-0001-5419-5761
                Article
                221
                10.1186/s40035-020-00221-2
                7689983
                33239064
                0cb5a2a0-620e-4c8d-9ba8-b0d1aff2689f
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 16 June 2020
                : 3 November 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003621, Ministry of Science, ICT and Future Planning;
                Award ID: 2018R1A2A2A15023219
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100003625, Ministry of Health and Welfare;
                Award ID: grant number: HI20C0253
                Award Recipient :
                Funded by: Medical Research Centre
                Award ID: 2017R1A5A2015395
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                Neurosciences
                neuroinflammation,neurodegenerative diseases,microglia,astrocytes
                Neurosciences
                neuroinflammation, neurodegenerative diseases, microglia, astrocytes

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