Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies
Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies
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DOI：
10.1016/s0002-9440(10)64781-5
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发表时间：
2000-11-01
影响因子：
6
通讯作者：
Trojanowski, JQ
中科院分区：
文献类型：
--
作者：
Duda, JE;Giasson, BI;Trojanowski, JQ
活性氮可能通过翻译后改变正常脑蛋白而在神经退行性疾病中发挥机械作用。为了支持这一假设，我们证明抗 3-硝基酪氨酸多克隆抗体可对突触核蛋白病的所有主要标志性病变进行染色，包括路易体痴呆中的路易体、路易体神经突和神经轴突球体、阿尔茨海默病的路易体变体以及 1 型脑铁积累的神经变性。如多系统萎缩中的神经胶质和神经元细胞质内含物。与这些病理病变的其他体外硝化成分（例如神经丝亚基和微管）相比，该抗体主要识别硝化α-突触核蛋白。总的来说，这些发现表明α-突触核蛋白在病理病变中被硝化。硝化α-突触核蛋白在多种细胞内内含物中的广泛存在表明氧化/硝化参与神经退行性疾病的发生和/或进展。
Reactive nitrogen species may play a mechanistic rot in neurodegenerative diseases by posttranslationally altering normal brain proteins. In support of this hypothesis, we demonstrate that an anti-3-nitrotyrosine polyclonal antibody stains all of the major hallmark lesions of synucleinopathies Including Lewy bodies, Lewy neurites and neuraxonal spheroids in dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and neurodegeneration with brain iron accumulation type 1, as well. as glial and neuronal cytoplasmic inclusions in multiple system atrophy. This antibody predominantly recognized nitrated alpha -synuclein when compared to other In vitro nitrated constituents of these pathological lesions, such as neurofilament subunits and microtubules, Collectively, these findings imply that alpha -synuclein is nitrated in pathological lesions. The widespread presence of nitrated alpha -synuclein in diverse intracellular inclusions suggests that oxidation/nitration is involved in the onset and/or progression of neurodegenerative diseases.