RESEARCH: Mouse model of alpha-synuclein

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Note that Multiple System Atrophy is believed to be a disorder involving the

protein alpha-synuclein so this research is very important to understanding

the underlying cause of neurodegeneration in MSA.

Regards,

Pam

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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.

Giasson BI, Duda JE, Quinn SM, Zhang B, Trojanowski JQ, Lee VM.

Center for Neurodegenerative Disease Research, Department of Pathology and

Laboratory Medicine, 3600 Spruce Street, University of Pennsylvania School

of

Medicine, 19104, Philadelphia, PA, USA

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 [PubMed - in process]