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Dopamine promotes formation and secretion of non-fibrillar alpha-synuclein oligomers
Experimental & Molecular Medicine ; : 216-222, 2011.
Artículo en Inglés | WPRIM | ID: wpr-187631
ABSTRACT
Parkinson's disease (PD) is characterized by selective and progressive degeneration of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SNpc) and by abnormal aggregation of alpha-synuclein. Previous studies have suggested that DA can interact with alpha-synuclein, thus modulating the aggregation process of this protein; this interaction may account for the selective vulnerability of DA neurons in patients with PD. However, the relationship between DA and alpha-synuclein, and the role in progressive degeneration of DA neurons remains elusive. We have shown that in the presence of DA, recombinant human alpha-synuclein produces non-fibrillar, SDS-resistant oligomers, while beta-sheet-rich fibril formation is inhibited. Pharmacologic elevation of the cytoplasmic DA level increased the formation of SDS-resistant oligomers in DA-producing neuronal cells. DA promoted alpha-synuclein oligomerization in intracellular vesicles, but not in the cytosol. Furthermore, elevation of DA levels increased secretion of alpha-synuclein oligomers to the extracellular space, but the secretion of monomers was not changed. DA-induced secretion of alpha-synuclein oligomers may contribute to the progressive loss of the dopaminergic neuronal population and the pronounced neuroinflammation observed in the SNpc in patients with PD.
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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Enfermedad de Parkinson / Sustancia Negra / Dopamina / Levodopa / Western Blotting / Línea Celular Tumoral / Alfa-Sinucleína / Neuronas Límite: Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2011 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Enfermedad de Parkinson / Sustancia Negra / Dopamina / Levodopa / Western Blotting / Línea Celular Tumoral / Alfa-Sinucleína / Neuronas Límite: Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2011 Tipo del documento: Artículo