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Prolyl Oligopeptidase Regulates Dopamine Transporter Phosphorylation in the Nigrostriatal Pathway of Mouse.
Julku, Ulrika H; Panhelainen, Anne E; Tiilikainen, Saija E; Svarcbahs, Reinis; Tammimäki, Anne E; Piepponen, T Petteri; Savolainen, Mari H; Myöhänen, Timo T.
Afiliación
  • Julku UH; Division of Pharmacology and Pharmacotherapy, University of Helsinki, Viikinkaari 5E, P.O. Box 56, 00014, Helsinki, Finland.
  • Panhelainen AE; Institute of Biotechnology, University of Helsinki, Viikinkaari 5D, P.O. Box 56, 00014, Helsinki, Finland.
  • Tiilikainen SE; Division of Pharmacology and Pharmacotherapy, University of Helsinki, Viikinkaari 5E, P.O. Box 56, 00014, Helsinki, Finland.
  • Svarcbahs R; Division of Pharmacology and Pharmacotherapy, University of Helsinki, Viikinkaari 5E, P.O. Box 56, 00014, Helsinki, Finland.
  • Tammimäki AE; Division of Pharmacology and Pharmacotherapy, University of Helsinki, Viikinkaari 5E, P.O. Box 56, 00014, Helsinki, Finland.
  • Piepponen TP; Division of Pharmacology and Pharmacotherapy, University of Helsinki, Viikinkaari 5E, P.O. Box 56, 00014, Helsinki, Finland.
  • Savolainen MH; Division of Pharmacology and Pharmacotherapy, University of Helsinki, Viikinkaari 5E, P.O. Box 56, 00014, Helsinki, Finland.
  • Myöhänen TT; Division of Pharmacology and Pharmacotherapy, University of Helsinki, Viikinkaari 5E, P.O. Box 56, 00014, Helsinki, Finland. timo.myohanen@helsinki.fi.
Mol Neurobiol ; 55(1): 470-482, 2018 01.
Article en En | MEDLINE | ID: mdl-27966077
Alpha-synuclein is the main component of Lewy bodies, a histopathological finding of Parkinson's disease. Prolyl oligopeptidase (PREP) is a serine protease that binds to α-synuclein and accelerates its aggregation in vitro. PREP enzyme inhibitors have been shown to block the α-synuclein aggregation process in vitro and in cellular models, and also to enhance the clearance of α-synuclein aggregates in transgenic mouse models. Moreover, PREP inhibitors have induced alterations in dopamine and metabolite levels, and dopamine transporter immunoreactivity in the nigrostriatal tissue. In this study, we characterized the role of PREP in the nigrostriatal dopaminergic and GABAergic systems of wild-type C57Bl/6 and PREP knockout mice, and the effects of PREP overexpression on these systems. Extracellular concentrations of dopamine and protein levels of phosphorylated dopamine transporter were increased and dopamine reuptake was decreased in the striatum of PREP knockout mice, suggesting increased internalization of dopamine transporter from the presynaptic membrane. Furthermore, PREP overexpression increased the level of dopamine transporters in the nigrostriatal tissue but decreased phosphorylated dopamine transporters in the striatum in wild-type mice. Our results suggest that PREP regulates the function of dopamine transporter, possibly by controlling the phosphorylation and transport of dopamine transporter into the striatum or synaptic membrane.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sustancia Negra / Serina Endopeptidasas / Cuerpo Estriado / Proteínas de Transporte de Dopamina a través de la Membrana Plasmática Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Mol Neurobiol Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sustancia Negra / Serina Endopeptidasas / Cuerpo Estriado / Proteínas de Transporte de Dopamina a través de la Membrana Plasmática Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Mol Neurobiol Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Estados Unidos