Hyperphosphorylation and insolubility of α-synuclein in transgenic mouse oligodendrocytes
Hyperphosphorylation and insolubility of α-synuclein in transgenic mouse oligodendrocytes
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DOI：
10.1093/embo-reports/kvf109
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发表时间：
2002-06-01
期刊：
影响因子：
7.7
通讯作者：
Haass, C
中科院分区：
文献类型：
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作者：
Kahle, PJ;Neumann, M;Haass, C
由α-突触核蛋白（alphaSYN）组成的（寡树突）胶质细胞胞质内含物表征多系统萎缩（MSA）。成熟的少突胶质细胞（OL）通常不表达alphaSYN，因此MSA病理可能由OL中alphaSYN的异常表达引起。为了研究alphaSYN在OL中的病理沉积，产生转基因小鼠，其中人野生型alphaSYN由蛋白脂质蛋白启动子驱动。在OL中检测到转基因alphaSYN，但没有检测到其他脑细胞类型。在光学显微镜水平上，转基因alphaSYN轮廓类似于神经胶质细胞质内含物。引人注目的是，alphaSYN S129处的诊断性过度磷酸化在转基因小鼠中重现。一个显着比例的转基因alphaSYN是洗涤剂不溶性的，在MSA患者。组织学和生物化学异常是疾病相关alphaSYN的特异性异常，因为对照绿色荧光蛋白完全可溶且均匀分布在OL细胞体和突起中。因此，异位表达alphaSYN在OLs可能启动MSA病理学的显着特征。
(Oligodendro)glial cytoplasmic inclusions composed of alpha-synuclein (alphaSYN) characterize multiple system atrophy (MSA). Mature oligodendrocytes (OLs) do not normally express alphaSYN, so MSA pathology may arise from aberrant expression of alphaSYN in OLs. To study pathological deposition of alphaSYN in OLs, transgenic mice were generated in which human wild-type alphaSYN was driven by a proteolipid protein promoter. Transgenic alphaSYN was detected in OLs but no other brain cell type. At the light microscopic level, the transgenic alphaSYN profiles resembled glial cytoplasmic inclusions. Strikingly, the diagnostic hyperphosphorylation at S129 of alphaSYN was reproduced in the transgenic mice. A significant proportion of the transgenic alphaSYN was detergent insoluble, as in MSA patients. The histological and biochemical abnormalities were specific for the disease-relevant alphaSYN because control green fluorescent protein was fully soluble and evenly distributed throughout OL cell bodies and processes. Thus, ectopic expression alphaSYN in OLs might initiate salient features of MSA pathology.