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阿尔茨海默病期间活性氧激活NLRP3炎性小体的关键机制及潜在影响

Key Mechanisms and Potential Implications of in NLRP3 Inflammasome Activation by Reactive Oxygen Species during Alzheimer's Disease.

作者信息

Cordaro Marika, Salinaro Angela Trovato, Siracusa Rosalba, D'Amico Ramona, Impellizzeri Daniela, Scuto Maria, Ontario Maria Laura, Cuzzocrea Salvatore, Di Paola Rosanna, Fusco Roberta, Calabrese Vittorio

机构信息

Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, 98125 Messina, Italy.

Department of Biomedical and Biotechnological Sciences, University of Catania, 95124 Catania, Italy.

出版信息

Antioxidants (Basel). 2021 Oct 22;10(11):1664. doi: 10.3390/antiox10111664.

Abstract

Alzheimer's disease (AD) is the principal cause of dementia, and its incidence increases with age. Altered antioxidant systems and inflammation have an important role in the etiology of neurodegenerative disorders. In this study, we evaluated the effects of , a nutritional mushroom with important antioxidant effects, in a rat model of AD. Animals were injected with 70 mg/Kg of AlCl3 daily for 6 weeks, and was administered daily by gavage. Before the experiment's end date, behavioral test training was performed. At the end of the study, behavioral changes were assessed, and the animals were euthanized. Brain tissues were harvested for further analysis. AlCl3 mainly accumulates in the hippocampus, the principal region of the brain involved in memory functions and learning. administration reduced behavioral changes and hippocampal neuronal degeneration. Additionally, it reduced phosphorylated Tau levels, aberrant APP overexpression, and β-amyloid accumulation. Moreover, decreased the pro-oxidative and pro-inflammatory hippocampal alterations induced by AD. In particular, it reduced the activation of the NLRP3 inflammasome components, usually activated by increased oxidative stress during AD. Collectively, our results showed that has protective effects on behavioral alteration and histological modification associated with AD due to the modulation of the oxidative and inflammatory pathways, as well as regulating cellular brain stress.

摘要

阿尔茨海默病(AD)是痴呆的主要病因,其发病率随年龄增长而增加。抗氧化系统改变和炎症在神经退行性疾病的病因中起重要作用。在本研究中,我们评估了具有重要抗氧化作用的营养蘑菇对AD大鼠模型的影响。动物每天注射70mg/Kg的AlCl3,持续6周,并通过灌胃每天给予(此处原文缺失具体物质名称)。在实验结束日期前,进行行为测试训练。在研究结束时,评估行为变化,并对动物实施安乐死。采集脑组织进行进一步分析。AlCl3主要积聚在海马体中,海马体是大脑中参与记忆功能和学习的主要区域。给予(此处原文缺失具体物质名称)可减少行为变化和海马神经元变性。此外,它降低了磷酸化Tau水平、异常APP过表达和β-淀粉样蛋白积累。此外,(此处原文缺失具体物质名称)减少了AD诱导的海马体促氧化和促炎改变。特别是,它降低了通常在AD期间因氧化应激增加而激活的NLRP3炎性小体成分的激活。总体而言,我们的结果表明,由于对氧化和炎症途径的调节以及调节细胞脑应激,(此处原文缺失具体物质名称)对与AD相关的行为改变和组织学改变具有保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9390/8615045/b041cd4245a5/antioxidants-10-01664-g001.jpg

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