Reformulating Pro-Oxidant Microglia in Neurodegeneration.

Autor: García-Revilla J; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. juangare79@gmail.com.; Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain. juangare79@gmail.com., Alonso-Bellido IM; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. isaalobel@gmail.com.; Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain. isaalobel@gmail.com., Burguillos MA; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. maburguillos@us.es.; Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain. maburguillos@us.es., Herrera AJ; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. ajherrera@us.es.; Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain. ajherrera@us.es., Espinosa-Oliva AM; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. anaespinosa@us.es.; Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain. anaespinosa@us.es., Ruiz R; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. rruizlaza@us.es.; Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain. rruizlaza@us.es., Cruz-Hernández L; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. luiscruzhernandez1994@gmail.com.; Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain. luiscruzhernandez1994@gmail.com., García-Domínguez I; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. irenegarcia391@gmail.com.; Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain. irenegarcia391@gmail.com., Roca-Ceballos MA; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. marian.roca.ceballos@gmail.com.; Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain. marian.roca.ceballos@gmail.com., Santiago M; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. msantiago@us.es.; Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain. msantiago@us.es., Rodríguez-Gómez JA; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. rodriguez@us.es.; Departament of Medical Physiology and Biophysics, Faculty of Medicine, University of Seville, 41009 Sevilla, Spain. rodriguez@us.es., Soto MS; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. msarmiento@us.es.; Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain. msarmiento@us.es., de Pablos RM; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. depablos@us.es.; Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain. depablos@us.es., Venero JL; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. jlvenero@us.es.; Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain. jlvenero@us.es.
Jazyk: angličtina
Zdroj: Journal of clinical medicine [J Clin Med] 2019 Oct 17; Vol. 8 (10). Date of Electronic Publication: 2019 Oct 17.
DOI: 10.3390/jcm8101719
Abstrakt: In neurodegenerative diseases, microglia-mediated neuroinflammation and oxidative stress are central events. Recent genome-wide transcriptomic analyses of microglial cells under different disease conditions have uncovered a new subpopulation named disease-associated microglia (DAM). These studies have challenged the classical view of the microglia polarization state's proinflammatory M1 (classical activation) and immunosuppressive M2 (alternative activation). Molecular signatures of DAM and proinflammatory microglia (highly pro-oxidant) have shown clear differences, yet a partial overlapping gene profile is evident between both phenotypes. The switch activation of homeostatic microglia into reactive microglia relies on the selective activation of key surface receptors involved in the maintenance of brain homeostasis (a.k.a. pattern recognition receptors, PRRs). Two relevant PRRs are toll-like receptors (TLRs) and triggering receptors expressed on myeloid cells-2 (TREM2), whose selective activation is believed to generate either a proinflammatory or a DAM phenotype, respectively. However, the recent identification of endogenous disease-related ligands, which bind to and activate both TLRs and TREM2, anticipates the existence of rather complex microglia responses. Examples of potential endogenous dual ligands include amyloid β, galectin-3, and apolipoprotein E. These pleiotropic ligands induce a microglia polarization that is more complicated than initially expected, suggesting the possibility that different microglia subtypes may coexist. This review highlights the main microglia polarization states under disease conditions and their leading role orchestrating oxidative stress.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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