首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein
Authors:Giasson Benoit I  Duda John E  Quinn Shawn M  Zhang Bin  Trojanowski John Q  Lee Virginia M-Y
Institution:Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, 3600 Spruce Street, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Abstract:alpha-Synucleinopathies are neurodegenerative disorders that range pathologically from the demise of select groups of nuclei to pervasive degeneration throughout the neuraxis. Although mounting evidence suggests that alpha-synuclein lesions lead to neurodegeneration, this remains controversial. To explore this issue, we generated transgenic mice expressing wild-type and A53T human alpha-synuclein in CNS neurons. Mice expressing mutant, but not wild-type, alpha-synuclein developed a severe and complex motor impairment leading to paralysis and death. These animals developed age-dependent intracytoplasmic neuronal alpha-synuclein inclusions paralleling disease onset, and the alpha-synuclein inclusions recapitulated features of human counterparts. Moreover, immunoelectron microscopy revealed that the alpha-synuclein inclusions contained 10-16 nm wide fibrils similar to human pathological inclusions. These mice demonstrate that A53T alpha-synuclein leads to the formation of toxic filamentous alpha-synuclein neuronal inclusions that cause neurodegeneration.
Keywords:
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号