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Pramipexole Reduces Phosphorylation of α-Synuclein at Serine-129
- Source :
- Journal of Molecular Neuroscience
- Publisher :
- Springer Nature
-
Abstract
- α-Synuclein is a central component of the pathogenesis of Parkinson’s disease (PD). Phosphorylation at serine-129 represents an important post-translational modification and constitutes the major form of the protein in Lewy bodies. Several kinases have been implicated in the phosphorylation of α-synuclein. The targeting of kinase pathways as a potential to influence the pathogenesis of PD is an important focus of attention, given that mutations of specific kinases (LRRK2 and PINK1) are causes of familial PD. Pramipexole (PPX) is a dopamine agonist developed for the symptomatic relief of PD. Several in vitro and in vivo laboratory studies have demonstrated that PPX exerts neuroprotective properties in model systems of relevance to PD. The present study demonstrates that PPX inhibits the phosphorylation of α-synuclein and that this is independent of dopamine receptor activation. PPX blocks the increase in phosphorylated α-synuclein induced by inhibition of the ubiquitin proteasomal system. The phosphorylation of α-synuclein occurs in part at least through casein kinase 2, and PPX in turn reduces the phosphorylation of this enzyme, thereby inhibiting its activity. Thus, PPX decreases the phosphorylation of α-synuclein, and this mechanism may contribute to its protective properties in PD models. Electronic supplementary material The online version of this article (doi:10.1007/s12031-013-0030-8) contains supplementary material, which is available to authorized users.
- Subjects :
- PINK1
macromolecular substances
Pharmacology
Dopamine agonist
Article
Antiparkinson Agents
03 medical and health sciences
chemistry.chemical_compound
Cellular and Molecular Neuroscience
Pramipexole
0302 clinical medicine
Cell Line, Tumor
Serine
medicine
Humans
Benzothiazoles
Phosphorylation
Neurodegeneration
Casein Kinase II
030304 developmental biology
α-Synuclein
Alpha-synuclein
0303 health sciences
Kinase
General Medicine
LRRK2
Symptomatic relief
Neuroprotection
nervous system diseases
Dopamine agonists
chemistry
nervous system
alpha-Synuclein
Parkinson’s disease
Casein kinase 2
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 08958696
- Volume :
- 51
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular Neuroscience
- Accession number :
- edsair.doi.dedup.....df72b7cfd3f078e1a1433e4f579e0fab
- Full Text :
- https://doi.org/10.1007/s12031-013-0030-8