Nunes Marielza Andrade, Toricelli Mariana, Schöwe Natalia Mendes, Malerba Helena Nascimento, Dong-Creste Karis Ester, Farah Daniela Moura Azevedo Tuma, De Angelis Katia, Irigoyen Maria Claudia, Gobeil Fernand, Araujo Viel Tânia, Buck Hudson Sousa
Department of Physiological Sciences, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo 01221-020, Brazil.
School of Arts, Sciences and Humanities, University of Sao Paulo, Sao Paulo 03828-080, Brazil.
Pharmaceuticals (Basel). 2020 Oct 1;13(10):288. doi: 10.3390/ph13100288.
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.
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 Aβ peptide deposition.
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.
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.
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.
阿尔茨海默病的主要特征是与记忆形成相关的脑区出现显著的神经退行性变。这种进行性神经退行性变会导致认知障碍、行为改变、功能残疾甚至死亡。我们的研究小组已在阿尔茨海默病（AD）实验模型中证实了激肽释放酶-激肽系统（KKS）的变化，但缺乏关于KKS在阿尔茨海默病中作用的证据。
为了回答这个问题，我们评估了激肽B2受体（BKB2R）改善AD特征的潜力，特别是记忆障碍、神经退行性变和Aβ肽沉积。
为了评估B2的作用，我们使用了用B2受体（B2R）激动剂和拮抗剂治疗的转基因阿尔茨海默病小鼠，并进行了行为和生化测试。此外，我们对野生型（WT）和转基因（TG）动物进行了海马脑片培养，在处理后分析细胞因子、神经营养因子脑源性神经营因子（BDNF）、活化星形胶质细胞标志物S100B的密度以及细胞死亡情况。
用B2R激动剂治疗可保留转基因小鼠的空间记忆并减少淀粉样斑块沉积。在海马脑片培养中，用B2R激动剂治疗可减少细胞死亡、神经炎症和S100B水平，并增加BDNF释放。
我们的结果表明，激肽释放酶-激肽系统通过激活B2R在阿尔茨海默病中发挥有益作用。因此，使用B2R激动剂可能是诊断为阿尔茨海默病患者的一种可能治疗选择。
