Giasson Benoit I, Forman Mark S, Higuchi Makoto, Golbe Lawrence I, Graves Charles L, Kotzbauer Paul T, Trojanowski John Q, Lee Virginia M-Y
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine.
Science. 2003 Apr 25;300(5619):636-40. doi: 10.1126/science.1082324.
Alpha-synuclein (alpha-syn) and tau polymerize into amyloid fibrils and form intraneuronal filamentous inclusions characteristic of neurodegenerative diseases. We demonstrate that alpha-syn induces fibrillization of tau and that coincubation of tau and alpha-syn synergistically promotes fibrillization of both proteins. The in vivo relevance of these findings is grounded in the co-occurrence of alpha-syn and tau filamentous amyloid inclusions in humans, in single transgenic mice that express A53T human alpha-syn in neurons, and in oligodendrocytes of bigenic mice that express wild-type human alpha-syn plus P301L mutant tau. This suggests that interactions between alpha-syn and tau can promote their fibrillization and drive the formation of pathological inclusions in human neurodegenerative diseases.
α-突触核蛋白（α-syn）和tau蛋白聚合成淀粉样原纤维，并在神经元内形成神经退行性疾病特有的丝状包涵体。我们证明α-syn可诱导tau蛋白纤维化，且tau蛋白与α-syn共同孵育可协同促进这两种蛋白的纤维化。这些发现与人类、在神经元中表达A53T人α-syn的单转基因小鼠以及表达野生型人α-syn加P301L突变型tau的双转基因小鼠的少突胶质细胞中α-syn和tau丝状淀粉样包涵体的共同出现相关。这表明α-syn与tau之间的相互作用可促进它们的纤维化，并在人类神经退行性疾病中驱动病理性包涵体的形成。
