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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Brain / metabolism*
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Brain / ultrastructure
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Dopamine / physiology*
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Humans
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Inclusion Bodies / metabolism*
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Inclusion Bodies / ultrastructure
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Lewy Bodies / ultrastructure
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Lewy Body Disease / metabolism
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Lewy Body Disease / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Mice, Transgenic
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Microscopy, Electron
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Motor Activity
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / immunology
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Nerve Tissue Proteins / metabolism*
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Neurodegenerative Diseases / metabolism*
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Neurodegenerative Diseases / pathology
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Neurons / metabolism*
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Neurons / ultrastructure
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Substantia Nigra / metabolism
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Substantia Nigra / ultrastructure
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Synucleins
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Tyrosine 3-Monooxygenase / immunology
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Tyrosine 3-Monooxygenase / metabolism
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Ubiquitins / metabolism
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alpha-Synuclein
Substances
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Nerve Tissue Proteins
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SNCA protein, human
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Snca protein, mouse
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Synucleins
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Ubiquitins
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alpha-Synuclein
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Tyrosine 3-Monooxygenase
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Dopamine