Axon pathology in Parkinson ’ s disease and Lewy body dementia hippocampus contains a-, b-, and g-synuclein
Axon pathology in Parkinson ’ s disease and Lewy body dementia hippocampus contains a-, b-, and g-synuclein
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帕金森病和路易体痴呆海马的轴突病理学包含 a-、b- 和 g-突触核蛋白
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发表时间：
1999
期刊：
影响因子：
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通讯作者：
J. Trojanowski
中科院分区：
文献类型：
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作者：
J. Galvin;K. Uryu;V. Lee;J. Trojanowski
致病性α-突触核蛋白（aS）基因突变发生在罕见的家族性帕金森病（PD）激酶中，并且野生型aS是散发性PD、伴有LB的痴呆（DLB）和阿尔茨海默病的LB变体中的路易体（LB）的主要组分，但是b-突触核蛋白（bS）和g-突触核蛋白（gS）尚未涉及神经系统疾病。在这里，我们表明，在PD和DLB，但不是正常的大脑，抗体的aS和bS揭示新的突触前轴突终端病理在海马齿状，门，和CA 2 y3地区，而抗体的GS检测以前未被识别的轴突球状体样病变在海马齿状分子层。aSand bS标记的门部营养不良神经突中其他突触蛋白和突触囊泡样结构的聚集表明突触功能障碍可能是由这些病变引起的。我们的发现拓宽了神经退行性“突触核蛋白病”的概念，除了aS之外，bS和gS也参与了PD和DLB的发病过程。
Pathogenic a-synuclein (aS) gene mutations occur in rare familial Parkinson’s disease (PD) kindreds, and wild-type aS is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer’s disease, but b-synuclein (bS) and g-synuclein (gS) have not yet been implicated in neurological disorders. Here we show that in PD and DLB, but not normal brains, antibodies to aS and bS reveal novel presynaptic axon terminal pathology in the hippocampal dentate, hilar, and CA2y3 regions, whereas antibodies to gS detect previously unrecognized axonal spheroid-like lesions in the hippocampal dentate molecular layer. The aggregation of other synaptic proteins and synaptic vesicle-like structures in the aSand bS-labeled hilar dystrophic neurites suggests that synaptic dysfunction may result from these lesions. Our findings broaden the concept of neurodegenerative ‘‘synucleinopathies’’ by implicating bS and gS, in addition to aS, in the onsetyprogression of PD and DLB.