Dopamine-dependent neurotoxicity of α-synuclein: A mechanism for selective neurodegeneration in Parkinson disease
| Autor: | Bruce A. Yankner, Frank J S Lee, Shyan Yuan Kao, Weihong Song, Lee-Way Jin, Jin Xu |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Pathology
medicine.medical_specialty Tyrosine 3-Monooxygenase Dopamine Neurotoxins Synucleins Apoptosis Nerve Tissue Proteins Substantia nigra Transfection Neuroprotection General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Tumor Cells Cultured medicine Humans Cells Cultured Neurons Alpha-synuclein chemistry.chemical_classification Reactive oxygen species Neurodegeneration Dopaminergic Neurotoxicity Parkinson Disease General Medicine Phosphoproteins medicine.disease nervous system diseases Cell biology Substantia Nigra Neuroprotective Agents 14-3-3 Proteins nervous system chemistry Nerve Degeneration alpha-Synuclein medicine.drug |
| Zdroj: | Nature Medicine. 8:600-606 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | The mechanism by which dopaminergic neurons are selectively lost in Parkinson disease (PD) is unknown. Here we show that accumulation of alpha-synuclein in cultured human dopaminergic neurons results in apoptosis that requires endogenous dopamine production and is mediated by reactive oxygen species. In contrast, alpha-synuclein is not toxic in non-dopaminergic human cortical neurons, but rather exhibits neuroprotective activity. Dopamine-dependent neurotoxicity is mediated by 54 83-kD soluble protein complexes that contain alpha-synuclein and 14-3-3 protein, which are elevated selectively in the substantia nigra in PD. Thus, accumulation of soluble alpha-synuclein protein complexes can render endogenous dopamine toxic, suggesting a potential mechanism for the selectivity of neuronal loss in PD. |
| Databáze: | OpenAIRE |
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