Galvin J E, Uryu K, Lee V M, Trojanowski J Q
Department of Neurology, Medical College of Pennsylvania, Hahnemann University, 245 North 15th Street, Philadelphia, PA 19129, USA.
Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13450-5. doi: 10.1073/pnas.96.23.13450.
Pathogenic alpha-synuclein (alphaS) gene mutations occur in rare familial Parkinson's disease (PD) kindreds, and wild-type alphaS is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer's disease, but beta-synuclein (betaS) and gamma-synuclein (gammaS) have not yet been implicated in neurological disorders. Here we show that in PD and DLB, but not normal brains, antibodies to alphaS and betaS reveal novel presynaptic axon terminal pathology in the hippocampal dentate, hilar, and CA2/3 regions, whereas antibodies to gammaS 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 alphaS- and betaS-labeled hilar dystrophic neurites suggests that synaptic dysfunction may result from these lesions. Our findings broaden the concept of neurodegenerative "synucleinopathies" by implicating betaS and gammaS, in addition to alphaS, in the onset/progression of PD and DLB.
致病性α-突触核蛋白（αS）基因突变发生于罕见的家族性帕金森病（PD）家系中，野生型αS是散发性PD、路易体痴呆（DLB）以及阿尔茨海默病路易体变异型中路易小体（LB）的主要成分，但β-突触核蛋白（βS）和γ-突触核蛋白（γS）尚未被证实与神经疾病有关。在此我们表明，在PD和DLB中，而非正常大脑中，针对αS和βS的抗体在海马齿状回、门区及CA2/3区域显示出新的突触前轴突终末病变，而针对γS的抗体则在海马齿状回分子层检测到先前未被识别的轴突样球状病变。在αS和βS标记的门区营养不良性神经突中其他突触蛋白和突触小泡样结构的聚集表明，这些病变可能导致突触功能障碍。我们的研究结果通过表明除αS外，βS和γS也参与PD和DLB的发病/进展，拓宽了神经退行性“突触核蛋白病”的概念。
