[HTML][HTML] Neuronal α-synucleinopathy with severe movement disorder in mice expressing A53T human α-synuclein

BI Giasson, JE Duda, SM Quinn, B Zhang… - Neuron, 2002 - cell.com
BI Giasson, JE Duda, SM Quinn, B Zhang, JQ Trojanowski, VMY Lee
Neuron, 2002cell.com
Abstract α-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 α-synuclein lesions lead to
neurodegeneration, this remains controversial. To explore this issue, we generated
transgenic mice expressing wild-type and A53T human α-synuclein in CNS neurons. Mice
expressing mutant, but not wild-type, α-synuclein developed a severe and complex motor …
Abstract
α-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 α-synuclein lesions lead to neurodegeneration, this remains controversial. To explore this issue, we generated transgenic mice expressing wild-type and A53T human α-synuclein in CNS neurons. Mice expressing mutant, but not wild-type, α-synuclein developed a severe and complex motor impairment leading to paralysis and death. These animals developed age-dependent intracytoplasmic neuronal α-synuclein inclusions paralleling disease onset, and the α-synuclein inclusions recapitulated features of human counterparts. Moreover, immunoelectron microscopy revealed that the α-synuclein inclusions contained 10–16 nm wide fibrils similar to human pathological inclusions. These mice demonstrate that A53T α-synuclein leads to the formation of toxic filamentous α-synuclein neuronal inclusions that cause neurodegeneration.
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