Nitrated α-Synuclein Induces the Loss of Dopaminergic Neurons in the Substantia Nigra of Rats
| Autor: | Zhongwang Yu, Xiao-Hui Xu, Cheng He, Chun Hu, Zhaohuan Zhang, Zhenghua Xiang, Jianfeng Zhou |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Pathology
medicine.medical_specialty Programmed cell death Neurite animal diseases Dopamine lcsh:Medicine Down-Regulation Substantia nigra Biology Pathogenesis chemistry.chemical_compound medicine Animals Biochemistry/Macromolecular Chemistry lcsh:Science Cells Cultured Gait Disorders Neurologic Alpha-synuclein Neurons Multidisciplinary Nitrates Cell Death Receptors Dopamine D2 Dopaminergic lcsh:R Biochemistry/Chemical Biology of the Cell Parkinson Disease Cell Biology/Cellular Death and Stress Responses nervous system diseases Rats Substantia Nigra chemistry nervous system alpha-Synuclein lcsh:Q Neuroscience/Neurobiology of Disease and Regeneration Immunostaining medicine.drug Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 4, p e9956 (2010) |
| ISSN: | 1932-6203 |
| Popis: | BACKGROUND: The pathology of Parkinson's disease (PD) is characterized by the degeneration of the nigrostriatal dopaminergic pathway, as well as the formation of intraneuronal inclusions known as Lewy bodies and Lewy neurites in the substantia nigra. Accumulations of nitrated alpha-synuclein are demonstrated in the signature inclusions of Parkinson's disease. However, whether the nitration of alpha-synuclein is relevant to the pathogenesis of PD is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, effect of nitrated alpha-synuclein to dopaminergic (DA) neurons was determined by delivering nitrated recombinant TAT-alpha-synuclein intracellular. We provide evidence to show that the nitrated alpha-synuclein was toxic to cultured dopaminergic SHSY-5Y neurons and primary mesencephalic DA neurons to a much greater degree than unnitrated alpha-synuclein. Moreover, we show that administration of nitrated alpha-synuclein to the substantia nigra pars compacta of rats caused severe reductions in the number of DA neurons therein, and led to the down-regulation of D(2)R in the striatum in vivo. Furthermore, when administered to the substantia nigra of rats, nitrated alpha-synuclein caused PD-like motor dysfunctions, such as reduced locomotion and motor asymmetry, however unmodified alpha-synuclein had significantly less severe behavioral effects. CONCLUSIONS/SIGNIFICANCE: Our results provide evidence that alpha-synuclein, principally in its nitrated form, induce DA neuron death and may be a major factor in the etiology of PD. |
| Databáze: | OpenAIRE |
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