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PLoS One. 2011;6(12):e27959. doi: 10.1371/journal.pone.0027959. Epub 2011 Dec 7.

Redistribution of DAT/α-synuclein complexes visualized by "in situ" proximity ligation assay in transgenic mice modelling early Parkinson's disease.

Author information

  • 1Division of Pharmacology, Department of Biomedical Sciences and Biotechnologies and National Institute of Neuroscience-Italy, School of Medicine, University of Brescia, Brescia, Italy. bellucci@med.unibs.it

Erratum in

  • PLoS One. 2012;7(1). doi:10.1371/annotation/58679d17-c619-4f13-b11f-146dacfe7e92. Grazia, Maria [corrected to Spillantini, Maria Grazia].

Abstract

Alpha-synuclein, the major component of Lewy bodies, is thought to play a central role in the onset of synaptic dysfunctions in Parkinson's disease (PD). In particular, α-synuclein may affect dopaminergic neuron function as it interacts with a key protein modulating dopamine (DA) content at the synapse: the DA transporter (DAT). Indeed, recent evidence from our "in vitro" studies showed that α-synuclein aggregation decreases the expression and membrane trafficking of the DAT as the DAT is retained into α-synuclein-immunopositive inclusions. This notwithstanding, "in vivo" studies on PD animal models investigating whether DAT distribution is altered by the pathological overexpression and aggregation of α-synuclein are missing. By using the proximity ligation assay, a technique which allows the "in situ" visualization of protein-protein interactions, we studied the occurrence of alterations in the distribution of DAT/α-synuclein complexes in the SYN120 transgenic mouse model, showing insoluble α-synuclein aggregates into dopaminergic neurons of the nigrostriatal system, reduced striatal DA levels and an altered distribution of synaptic proteins in the striatum. We found that DAT/α-synuclein complexes were markedly redistributed in the striatum and substantia nigra of SYN120 mice. These alterations were accompanied by a significant increase of DAT striatal levels in transgenic animals when compared to wild type littermates. Our data indicate that, in the early pathogenesis of PD, α-synuclein acts as a fine modulator of the dopaminergic synapse by regulating the subcellular distribution of key proteins such as the DAT.

PMID:
22163275
[PubMed - indexed for MEDLINE]
PMCID:
PMC3233557
Free PMC Article

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