RGD Reference Report - Selenoprotein T Exerts an Essential Oxidoreductase Activity That Protects Dopaminergic Neurons in Mouse Models of Parkinson's Disease. - Rat Genome Database

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Selenoprotein T Exerts an Essential Oxidoreductase Activity That Protects Dopaminergic Neurons in Mouse Models of Parkinson's Disease.

Authors: Boukhzar, Loubna  Hamieh, Abdallah  Cartier, Dorthe  Tanguy, Yannick  Alsharif, Ifat  Castex, Matthieu  Arabo, Arnaud  El Hajji, Sana  Bonnet, Jean-Jacques  Errami, Mohammed  Falluel-Morel, Anthony  Chagraoui, Abdeslam  Lihrmann, Isabelle  Anouar, Youssef 
Citation: Boukhzar L, etal., Antioxid Redox Signal. 2016 Apr 10;24(11):557-74. doi: 10.1089/ars.2015.6478. Epub 2016 Mar 16.
RGD ID: 12793008
Pubmed: (View Article at PubMed) PMID:26866473
DOI: Full-text: DOI:10.1089/ars.2015.6478


AIMS: Oxidative stress is central to the pathogenesis of Parkinson's disease (PD), but the mechanisms involved in the control of this stress in dopaminergic cells are not fully understood. There is increasing evidence that selenoproteins play a central role in the control of redox homeostasis and cell defense, but the precise contribution of members of this family of proteins during the course of neurodegenerative diseases is still elusive.
RESULTS: We demonstrated first that selenoprotein T (SelT) whose gene disruption is lethal during embryogenesis, exerts a potent oxidoreductase activity. In the SH-SY5Y cell model of dopaminergic neurons, both silencing and overexpression of SelT affected oxidative stress and cell survival. Treatment with PD-inducing neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or rotenone triggered SelT expression in the nigrostriatal pathway of wild-type mice, but provoked rapid and severe parkinsonian-like motor defects in conditional brain SelT-deficient mice. This motor impairment was associated with marked oxidative stress and neurodegeneration and decreased tyrosine hydroxylase activity and dopamine levels in the nigrostriatal system. Finally, in PD patients, we report that SelT is tremendously increased in the caudate putamen tissue.
INNOVATION: These results reveal the activity of a novel selenoprotein enzyme that protects dopaminergic neurons against oxidative stress and prevents early and severe movement impairment in animal models of PD.
CONCLUSIONS: Our findings indicate that selenoproteins such as SelT play a crucial role in the protection of dopaminergic neurons against oxidative stress and cell death, providing insight into the molecular underpinnings of this stress in PD.

Annotation

Gene Ontology Annotations    

Biological Process

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Selenot  (selenoprotein T)


Additional Information