Dopaminergic loss and inclusion body formation in α-synuclein mice:: Implications for neurodegenerative disorders
Dopaminergic loss and inclusion body formation in α-synuclein mice:: Implications for neurodegenerative disorders
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DOI：
10.1126/science.287.5456.1265
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发表时间：
2000-02-18
期刊：
影响因子：
56.9
通讯作者：
Mucke, L
中科院分区：
文献类型：
--
作者：
Masliah, E;Rockenstein, E;Mucke, L
为了阐明突触蛋白α-突触核蛋白在神经退行性疾病中的作用，产生表达野生型人α-突触核蛋白的转基因小鼠。人α-突触核蛋白的神经元表达导致新皮层、海马和黑质神经元中α-突触核蛋白和泛素免疫反应性包涵体的进行性积累。超微结构分析显示电子致密的核内沉积物和细胞质内含物。这些改变与基底神经节中多巴胺能末梢的丢失和运动障碍有关。这些结果表明，野生型α-突触核蛋白的积累可能在帕金森病和相关疾病中起因果作用。
To elucidate the role of the synaptic protein alpha-synuclein in neurodegenerative disorders, transgenic mice expressing wild-type human alpha-synuclein were generated. Neuronal expression of human alpha-synuclein resulted in progressive accumulation of alpha-synuclein-and ubiquitin-immunoreactive inclusions in neurons in the neocortex, hippocampus, and substantia nigra. Ultrastructural analysis revealed both electron-dense intranuclear deposits and cytoplasmic inclusions. These alterations were associated with Loss of dopaminergic terminals in the basal ganglia and with motor impairments. These results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions.