Kahle Philipp J, Neumann Manuela, Ozmen Laurence, Muller Veronika, Jacobsen Helmut, Spooren Will, Fuss Babette, Mallon Barbara, Macklin Wendy B, Fujiwara Hideo, Hasegawa Masato, Iwatsubo Takeshi, Kretzschmar Hans A, Haass Christian
Laboratory for Alzheimer's and Parkinson's Disease Research, Department of Biochemistry, Ludwig Maximilians University, D-80336 Munich, Germany.
EMBO Rep. 2002 Jun;3(6):583-8. doi: 10.1093/embo-reports/kvf109. Epub 2002 May 24.
(Oligodendro)glial cytoplasmic inclusions composed of alpha-synuclein (alpha SYN) characterize multiple system atrophy (MSA). Mature oligodendrocytes (OLs) do not normally express alpha SYN, so MSA pathology may arise from aberrant expression of alpha SYN in OLs. To study pathological deposition of alpha SYN in OLs, transgenic mice were generated in which human wild-type alpha SYN was driven by a proteolipid protein promoter. Transgenic alpha SYN was detected in OLs but no other brain cell type. At the light microscopic level, the transgenic alpha SYN profiles resembled glial cytoplasmic inclusions. Strikingly, the diagnostic hyperphosphorylation at S129 of alpha SYN was reproduced in the transgenic mice. A significant proportion of the transgenic alpha SYN was detergent insoluble, as in MSA patients. The histological and biochemical abnormalities were specific for the disease-relevant alpha SYN because control green fluorescent protein was fully soluble and evenly distributed throughout OL cell bodies and processes. Thus, ectopic expression alpha SYN in OLs might initiate salient features of MSA pathology.
由α-突触核蛋白（α-SYN）组成的（少突）胶质细胞质内含物是多系统萎缩（MSA）的特征。成熟的少突胶质细胞（OLs）通常不表达α-SYN，因此MSA病理可能源于OLs中α-SYN的异常表达。为了研究α-SYN在OLs中的病理沉积，构建了转基因小鼠，其中人野生型α-SYN由蛋白脂质蛋白启动子驱动。在OLs而非其他脑细胞类型中检测到转基因α-SYN。在光学显微镜水平上，转基因α-SYN形态类似于胶质细胞质内含物。引人注目的是，转基因小鼠中再现了α-SYN在S129处的诊断性过度磷酸化。与MSA患者一样，相当一部分转基因α-SYN不溶于去污剂。组织学和生化异常是疾病相关α-SYN所特有的，因为对照绿色荧光蛋白完全可溶并均匀分布于整个OL细胞体和突起中。因此，OLs中α-SYN的异位表达可能引发MSA病理的显著特征。
