Roles of oxidative stresses in neurodegeneration and myodegeneration focusing on the heme catabolism

氧化应激在神经变性和肌变性中的作用，重点关注血红素分解代谢

• 批准号: 12670588
• 负责人: TAKEDA Atsushi
• 金额: $ 1.98万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670588/
• 关键词: oxidative stresses; RNA oxidation; nucleic acid oxidation; Alzheimer disease; Parkinson disease; multiple system atrophy; heme oxygenase; Parkinson disease; Alzheimer disease; bilirubin; biopyrrin; alpha-synuclein; oxidative stress; neurodege

Through this project, we revealed that increased levels of RNA oxidation were commonly observed in brains affected with neurodegenerative diseases including Alzheimer disease, Parkinson disease and dementia with Lewy bodies. The oxidized RNAs were prominently identified in the affected brain lesions in their early stages, and were decreased wish the progression of diseases. Furthermore, the end product of RNA oxidation, 8-hydroxy guanosine (8OHG), was increased in the serum and CSF samples of Parkinson disease and multiple system atrophies. It is suggested that the levels of 8OHG can be applied for the diagnostic biomarker of neurodegenerative diseases.We also identified that the RNA oxidation was associated wish the degenerative changes in smyopathies wish rimmed vacuoles. Through our investigation, it was shown that oxidative stresses might play a key roles in myodegeneration.

通过这个项目，我们发现，在患有神经退行性疾病（包括阿尔茨海默病、帕金森病和路易体痴呆症）的大脑中，通常观察到 RNA 氧化水平升高。氧化的RNA在早期受影响的脑损伤中被显着识别，并且随着疾病的进展而减少。此外，RNA氧化的最终产物8-羟基鸟苷（8OHG）在帕金森病和多系统萎缩的血清和脑脊液样本中增加。建议8OHG水平可用作神经退行性疾病的诊断生物标志物。我们还发现RNA氧化与肌病边缘空泡的退行性变化有关。通过我们的调查，结果表明氧化应激可能在肌变性中发挥关键作用。

项目成果

Nunomura A., Chiba A., Kosaka K., Takeda A., Castellani RJ., Smith MA., Perry G: "Neuronal RNA oxidation is a prominent feature of dementia with Lewy bodies."Neuro Report. 13. 2035-2039 (2002)

Nunomura A.、Chiba A.、Kosaka K.、Takeda A.、Castellani RJ.、Smith MA.、Perry G：“神经元 RNA 氧化是路易体痴呆的一个突出特征。”《神经报告》。

Kikuchi A., et al.: "Hypoperfusion in the supplementary motor area, dorsolateral prefrontal cortex and insular cortex in Parkinson's disease"Journal of Neurologial Science. 193. 29-36 (2001)

Kikuchi A. 等人：“帕金森病中辅助运动区、背外侧前额皮质和岛叶皮质的灌注不足”《神经科学杂志》。

Castellani RJ., Hirai K., Aliev G., Drew KL., Nunomura A., Takeda A., Cashi AD., Obrenovich ME., Perry G., Smith MA.: "Role of mitachondrial dysfunction in Alzheimer disease."J. Neuroscience Research. 70. 357-360 (2002)

Castellani RJ.、Hirai K.、Aliev G.、Drew KL.、Nunomura A.、Takeda A.、Cashi AD.、Obrenovich ME.、Perry G.、Smith MA.：“线粒体功能障碍在阿尔茨海默病中的作用。”

Perry G., Nunomura A., Hirai K., Zhu X., Perz M., Avila J., Castellani RJ., Atwood CS., Aliev G., Sayre LM., Takeda A., Smith MA.: "Is oxidative damage the fundamental pathogenic mechanism of Alzheimer's and other neurodegenerative diseases?"Free Radical

Perry G.、Nunomura A.、Hirai K.、Zhu X.、Perz M.、Avila J.、Castellani RJ.、Atwood CS.、Aliev G.、Sayre LM.、Takeda A.、Smith MA.：“是

Tateyama M., Takeda A., Onodera Y., Matsuzaki M., Hasegawa Y., Nunomura A., Hirai K., Perry G., Smith MA., Itoyama Y.: "Oxidative stress and predominant Abeta42(43) deposition in myopathies with rimmed vacuoles."Acta Neuropathologica. 105. 581-585 (2003)

Tateyama M.、Takeda A.、Onodera Y.、Matsuzaki M.、Hasekawa Y.、Nunomura A.、Hirai K.、Perry G.、Smith MA.、Itoyama Y.：“氧化应激和主要 Abeta42(43) 沉积