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Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders.

Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for... To elucidate the role of the synaptic protein alpha-synuclein in neurodegenerative disorders, transgenic mice expressing wild-type human alpha-synuclein were generated. Neuronal expression of human alpha-synuclein resulted in progressive accumulation of alpha-synuclein-and ubiquitin-immunoreactive inclusions in neurons in the neocortex, hippocampus, and substantia nigra. Ultrastructural analysis revealed both electron-dense intranuclear deposits and cytoplasmic inclusions. These alterations were associated with loss of dopaminergic terminals in the basal ganglia and with motor impairments. These results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Science (New York, N.Y.) Pubmed

Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders.

Science (New York, N.Y.) , Volume 287 (5456): -1255 – Mar 6, 2000

Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders.


Abstract

To elucidate the role of the synaptic protein alpha-synuclein in neurodegenerative disorders, transgenic mice expressing wild-type human alpha-synuclein were generated. Neuronal expression of human alpha-synuclein resulted in progressive accumulation of alpha-synuclein-and ubiquitin-immunoreactive inclusions in neurons in the neocortex, hippocampus, and substantia nigra. Ultrastructural analysis revealed both electron-dense intranuclear deposits and cytoplasmic inclusions. These alterations were associated with loss of dopaminergic terminals in the basal ganglia and with motor impairments. These results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions.

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References (23)

ISSN
0036-8075
DOI
10.1126/science.287.5456.1265
pmid
10678833

Abstract

To elucidate the role of the synaptic protein alpha-synuclein in neurodegenerative disorders, transgenic mice expressing wild-type human alpha-synuclein were generated. Neuronal expression of human alpha-synuclein resulted in progressive accumulation of alpha-synuclein-and ubiquitin-immunoreactive inclusions in neurons in the neocortex, hippocampus, and substantia nigra. Ultrastructural analysis revealed both electron-dense intranuclear deposits and cytoplasmic inclusions. These alterations were associated with loss of dopaminergic terminals in the basal ganglia and with motor impairments. These results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions.

Journal

Science (New York, N.Y.)Pubmed

Published: Mar 6, 2000

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