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Neuron. 2002 May 16;34(4):521-33.

Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein.

Author information

1
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.

PMID:
12062037
[Indexed for MEDLINE]
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