| First Author | Giasson BI | Year | 2002 |
| Journal | Neuron | Volume | 34 |
| Issue | 4 | Pages | 521-33 |
| PubMed ID | 12062037 | Mgi Jnum | J:76657 |
| Mgi Id | MGI:2179902 | Doi | 10.1016/s0896-6273(02)00682-7 |
| Citation | Giasson BI, et al. (2002) Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34(4):521-33 |
| abstractText | 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. |
