Striatal oxidative damages and neuroinflammation correlate with progression and survival of Lewy body and Alzheimer diseases.
Striatal oxidative damages and neuroinflammation correlate with progression and survival of Lewy body and Alzheimer diseases.
复制标题
纹状体氧化的损害和神经炎症与路易体和阿尔茨海默氏病的进展和存活相关。
DOI：
10.4103/1673-5374.322463
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发表时间：
2022-04
影响因子：
6.1
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Li H;Knight WC;Xu J
神经退行性疾病是一类慢性和复杂的疾病，其特征在于不同脑区域中的神经元的进行性损失。神经退行性疾病进展的机制尚未完全阐明。在这项观察性研究中，我们检查了路易体病（LBD）和阿尔茨海默病（AD）患者尾状核和壳核的各种生化参数，揭示了氧化损伤和神经炎症在晚期神经退行性变中的作用。我们进行了斯皮尔曼和Mantel-Cox分析，以研究氧化应激和神经炎症如何对疾病进展和生存产生综合影响。LBD的疾病进展与LBD队列纹状体中髓样细胞2水平上表达的聚（ADP-核糖）和触发受体呈正相关，表明潜在的死亡是疾病进展恶化的主要特征，可能有助于转换小胶质细胞炎症表型。AD的疾病进展与纹状体中的8-氧代-7，8-二氢-2 ′-脱氧鸟苷（8-oxo-dG）和髓过氧化物酶浓度呈负相关，表明可能的线粒体功能障碍可能通过β-淀粉样蛋白进入线粒体和随后的自由基产生的机制参与AD的进展。纹状体8-oxo-dG和髓过氧化物酶水平较低的患者在AD中具有生存优势。发病年龄也影响疾病进展。尸检生物化学、遗传学和放射自显影研究的组织申请由华盛顿大学阿尔茨海默病研究中心（ADRC）生物标本委员会批准（伦理批准参考编号：T1705，批准日期：2019年8月6日）。重组DNA和危险研究材料获得华盛顿大学环境健康与安全生物安全委员会批准（批准代码：3739，批准日期：2020年2月25日）。放射性物质授权由华盛顿大学环境健康与安全辐射安全委员会批准（批准代码：1056，批准日期：2019年9月18日）。
Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain areas. The mechanisms responsible for the disease progression in neurodegeneration are not fully illustrated. In this observational study, we have examined diverse biochemical parameters in the caudate and putamen of patients with Lewy body diseases (LBDs) and Alzheimer disease (AD), shedding some light on the involvement of oxidative damage and neuroinflammation in advanced neurodegeneration. We performed Spearman and Mantel-Cox analyses to investigate how oxidative stress and neuroinflammation exert comprehensive effects on disease progression and survival. Disease progression in LBDs correlated positively with poly (ADP-Ribose) and triggering receptors expressed on myeloid cell 2 levels in the striatum of LBD cohorts, indicating that potential parthanatos was a dominant feature of worsening disease progression and might contribute to switching microglial inflammatory phenotypes. Disease progression in AD corresponds negatively with 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) and myeloperoxidase concentrations in the striatum, suggesting that possible mitochondria dysfunction may be involved in the progression of AD via a mechanism of β-amyloid entering the mitochondria and subsequent free radicals generation. Patients with lower striatal 8-oxo-dG and myeloperoxidase levels had a survival advantage in AD. The age of onset also affected disease progression. Tissue requests for the postmortem biochemistry, genetics, and autoradiography studies were approved by the Washington University Alzheimer’s Disease Research Center (ADRC) Biospecimens Committee (ethics approval reference number: T1705, approval date: August 6, 2019). Recombinant DNA and Hazardous Research Materials were approved by the Washington University Environmental Health & Safety Biological Safety Committee (approval code: 3739, approval date: February 25, 2020). Radioactive Material Authorization was approved by the Washington University Environmental Health & Safety Radiation Safety Committee (approval code: 1056, approval date: September 18, 2019).
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通讯作者：
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