文章基本信息

标题：Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein
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作者：Paula Desplats ; He-Jin Lee ; Eun-Jin Bae 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：31
页码：13010-13015
DOI：10.1073/pnas.0903691106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Neuronal accumulation of {alpha}-synuclein and Lewy body formation are characteristic to many neurodegenerative diseases, including Parkinson's disease (PD). This Lewy pathology appears to spread throughout the brain as the disease progresses. Furthermore, recent studies showed the occurrence of Lewy pathology in neurons grafted into the brains of PD patients, suggesting the spread of pathology from the host tissues to the grafts. The mechanism underlying this propagation is unknown. Here, we show that {alpha}-synuclein is transmitted via endocytosis to neighboring neurons and neuronal precursor cells, forming Lewy-like inclusions. Moreover, {alpha}-synuclein was transmitted from the affected neurons to engrafted neuronal precursor cells in a transgenic model of PD-like pathology. Failure of the protein quality control systems, especially lysosomes, promoted the accumulation of transmitted {alpha}-synuclein and inclusion formation. Cells exposed to neuron-derived {alpha}-synuclein showed signs of apoptosis, such as nuclear fragmentation and caspase 3 activation, both in vitro and in vivo. These findings demonstrate the cell-to-cell transmission of {alpha}-synuclein aggregates and provide critical insights into the mechanism of pathological progression in PD and other proteinopathies.
关键词：Lewy body ; neurodegeneration ; Parkinson's disease ; protein aggregation