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Neuroimmunology in experimental models of Autoimmune Encephalomyelitis and Congenital Zika Syndrome: physiopathogenesis, susceptibility, cellular therapy, vaccination

Abstract

Diseases of the central nervous system, either autoimmune, degenerative or infectious, are highly complex and debilitating. On one side, the extension of the life expectancy, uncontrolled diets and sedentarism have greatly contributed to the increased prevalence of these diseases on the population, as Alzheimer, Multiple Sclerosis and Parkinson Disease. On the other side, the spread of pathogens, mainly viruses that cause hemorrhagic diseases or Encephalitis are of major concern. Viruses as Ebola, Rift Valey, Dengue, Yellow Fever, and more recently Chikungunya and Zika, are great problems for public health, and must considered priorities. On both contexts, it is unquestionable the interaction between the central nervous system and the immune system. In fact, the field of neuroimmunology has widely broadened, bringing interesting answers. Now we know that important diseases as Colitis and Diabetes, as well as the Metabolic Syndrome and insulin resistance during Obesity, are well orchestrated by neuroimmune mechanisms. Along with that, it is noteworthy the great importance of the gut microbiota on that. Thus, it is very evident the importance of research in neuroimmunology. This may not only bring important information concerning the physiopathogenesis of the diseases, but also to support further applied approaches, as therapies and vaccines. In this context, in this project, we aim to understand several different aspects of the pathogenesis of the neuroinflammatory diseases using the models of Experimental Autoimmune Encephalomyelitis and the Zika Congenital Syndrome. We search for genes that confer resistance or susceptibility ZIKV infection, as well as for the miRNAs that modulate their expression. On the EAE model, we continue focused on understanding the role of the NMDAR on lymphocytes, studying not only its activation, but its maturation and function on the thymus and lamina propria, respectively. Furthermore, we propose a therapeutic approach to EAE using mesenchymal stem cells, and a vaccine platform against ZIKV, using a DNA plasmid. The results obtained will not only contribute to a better understanding on the pathogenesis of the diseases, but also support applied studies, and then, reduce their impact on the population. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BRANDAO, W. N.; DE OLIVEIRA, M. G.; ANDREONI, R. T.; NAKAYA, H.; FARIAS, A. S.; PERON, J. P. S. Neuroinflammation at single cell level: What is new?. Journal of Leukocyte Biology, AUG 2020. Web of Science Citations: 0.
GIOVANNONI, FEDERICO; BOSCH, IRENE; POLONIO, CAROLINA MANGANELI; TORTI, MARIA F.; WHEELER, MICHAEL A.; LI, ZHAORONG; ROMORINI, LEONARDO; RODRIGUEZ VARELA, MARIA S.; ROTHHAMMER, VEIT; BARROSO, ANDREIA; TJON, EMILY C.; SANMARCO, LILIANA M.; TAKENAKA, MAISA C.; MODARESI, SEYED MOHAMAD SADEGH; GUTIERREZ-VAZQUEZ, CRISTINA; ZANLUQUI, NAGELA GHABDAN; DOS SANTOS, NILTON BARRETO; MUNHOZ, CAROLINA DEMARCHI; WANG, ZHONGYAN; DAMONTE, ELSA B.; SHERR, DAVID; GEHRKE, LEE; SCHATZMANN PERON, JEAN PIERRE; GARCIA, CYBELE C.; QUINTANA, FRANCISCO J. AHR is a Zika virus host factor and a candidate target for antiviral therapy. NATURE NEUROSCIENCE, v. 23, n. 8 JUL 2020. Web of Science Citations: 1.
JEAN PIERRE SCHATZMANN PERON; HELDER NAKAYA. Susceptibility of the Elderly to SARS-CoV-2 Infection: ACE-2 Overexpression, Shedding, and Antibody-dependent Enhancement (ADE). Clinics, v. 75, p. -, 2020. Web of Science Citations: 1.
BRANDAO, WESLEY NOGUEIRA; ANDERSEN, MONICA LEVY; PALERMO-NETO, JOAO; PERON, JEAN PIERRE; ZAGER, ADRIANO. Therapeutic treatment with Modafinil decreases the severity of experimental autoimmune encephalomyelitis in mice. International Immunopharmacology, v. 75, OCT 2019. Web of Science Citations: 0.
OLIVEIRA, LILIAN G.; SCHATZMANN PERON, JEAN PIERRE. Viral receptors for flaviviruses: Not only gatekeepers. Journal of Leukocyte Biology, v. 106, n. 3, SI, p. 695-701, SEP 2019. Web of Science Citations: 1.

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