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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Kinin B2 Receptor Activation Prevents the Evolution of Alzheimer's Disease Pathological Characteristics in a Transgenic Mouse Model

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Author(s):
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Nunes, Marielza Andrade [1] ; Toricelli, Mariana [1] ; Schowe, Natalia Mendes [2] ; Malerba, Helena Nascimento [2] ; Dong-Creste, Karis Ester [1] ; Azevedo Tuma Farah, Daniela Moura [3, 4] ; De Angelis, Katia [5, 3] ; Irigoyen, Maria Claudia [4] ; Gobeil, Fernand [6] ; Viel, Tania Araujo [2] ; Buck, Hudson Sousa [1]
Total Authors: 11
Affiliation:
[1] Santa Casa de Sao Paulo Sch Med Sci, Dept Physiol Sci, BR-01221020 Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Arts Sci & Humanities, BR-03828080 Sao Paulo - Brazil
[3] Fed Univ Sao Paulo UNIFESP, Dept Physiol, BR-04023901 Sao Paulo - Brazil
[4] Univ Sao Paulo, Heart Inst Incor, Hypertens Unit, BR-05403900 Sao Paulo - Brazil
[5] Univ Nove Julho UNINOVE, Translat Physiol Lab, BR-01504001 Sao Paulo - Brazil
[6] Univ Sherbrooke, Dept Pharmacol & Physiol, Sherbrooke, PQ J1H 5N4 - Canada
Total Affiliations: 6
Document type: Journal article
Source: PHARMACEUTICALS; v. 13, n. 10 OCT 2020.
Web of Science Citations: 0
Abstract

Background: Alzheimer's disease is mainly characterized by remarkable neurodegeneration in brain areas related to memory formation. This progressive neurodegeneration causes cognitive impairment, changes in behavior, functional disability, and even death. Our group has demonstrated changes in the kallikrein-kinin system (KKS) in Alzheimer's disease (AD) experimental models, but there is a lack of evidence about the role of the KKS in Alzheimer's disease. Aim: In order to answer this question, we evaluated the potential of the kinin B2 receptors (BKB2R) to modify AD characteristics, particularly memory impairment, neurodegeneration, and A beta peptide deposition. Methods: To assess the effects of B2, we used transgenic Alzheimer's disease mice treated with B2 receptor (B2R) agonists and antagonists, and performed behavioral and biochemical tests. In addition, we performed organotypic hippocampal culture of wild-type (WT) and transgenic (TG) animals, where the density of cytokines, neurotrophin BDNF, activated astrocyte marker S100B, and cell death were analyzed after treatments. Results: Treatment with the B2R agonist preserved the spatial memory of transgenic mice and decreased amyloid plaque deposition. In organotypic hippocampal culture, treatment with B2R agonist decreased cell death, neuroinflammation, and S100B levels, and increased BDNF release. Conclusions: Our results indicate that the kallikrein-kinin system plays a beneficial role in Alzheimer's disease through B2R activation. The use of B2R agonists could, therefore, be a possible therapeutic option for patients diagnosed with Alzheimer's disease. (AU)

FAPESP's process: 13/13656-1 - Study of the neuroprotective role of kinin B2 receptor in the Alzheimer's Disease
Grantee:Hudson de Sousa Buck
Support type: Regular Research Grants
FAPESP's process: 17/21655-6 - Study of the cell survival modulation by B2 receptor for bradykinin and its impact on neuroinflamation in organotypic hippocampal culture of transgenic mice for Alzheimer's disease.
Grantee:Mariana Toricelli Pinto
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 16/07115-6 - Translational study of strategies and biomarkers to promote healthspan
Grantee:Tânia Araújo Viel
Support type: Regular Research Grants