Julku_2018_Mol.Neurobiol_55_470

Reference

Title : Prolyl Oligopeptidase Regulates Dopamine Transporter Phosphorylation in the Nigrostriatal Pathway of Mouse - Julku_2018_Mol.Neurobiol_55_470
Author(s) : Julku UH , Panhelainen AE , Tiilikainen SE , Svarcbahs R , Tammimaki AE , Piepponen TP , Savolainen MH , Myohanen TT
Ref : Molecular Neurobiology , 55 :470 , 2018
Abstract :

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 alpha-synuclein and accelerates its aggregation in vitro. PREP enzyme inhibitors have been shown to block the alpha-synuclein aggregation process in vitro and in cellular models, and also to enhance the clearance of alpha-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.

PubMedSearch : Julku_2018_Mol.Neurobiol_55_470
PubMedID: 27966077

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Citations formats

Julku UH, Panhelainen AE, Tiilikainen SE, Svarcbahs R, Tammimaki AE, Piepponen TP, Savolainen MH, Myohanen TT (2018)
Prolyl Oligopeptidase Regulates Dopamine Transporter Phosphorylation in the Nigrostriatal Pathway of Mouse
Molecular Neurobiology 55 :470

Julku UH, Panhelainen AE, Tiilikainen SE, Svarcbahs R, Tammimaki AE, Piepponen TP, Savolainen MH, Myohanen TT (2018)
Molecular Neurobiology 55 :470