title: Selenoprotein T Exerts an Essential Oxidoreductase Activity That Protects Dopaminergic Neurons in Mouse Models of Parkinson's Disease.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: 1 Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , Mont-Saint-Aignan, France .|2 Com UE, Normandy University of Rouen , France .|3 Institute for Research and Innovation in Biomedicine, University of Rouen , Mont-Saint-Aignan, Rouen, France .
authors: Loubna
authors: L
authors: Boukhzar
authors: 1 Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , Mont-Saint-Aignan, France .|2 Com UE, Normandy University of Rouen , France .|3 Institute for Research and Innovation in Biomedicine, University of Rouen , Mont-Saint-Aignan, Rouen, France .
authors: Abdallah
authors: A
authors: Hamieh
authors: 1 Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , Mont-Saint-Aignan, France .|2 Com UE, Normandy University of Rouen , France .|3 Institute for Research and Innovation in Biomedicine, University of Rouen , Mont-Saint-Aignan, Rouen, France .
authors: Dorthe
authors: D
authors: Cartier
authors: 1 Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , Mont-Saint-Aignan, France .|2 Com UE, Normandy University of Rouen , France .|3 Institute for Research and Innovation in Biomedicine, University of Rouen , Mont-Saint-Aignan, Rouen, France .
authors: Yannick
authors: Y
authors: Tanguy
authors: 1 Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , Mont-Saint-Aignan, France .|2 Com UE, Normandy University of Rouen , France .|3 Institute for Research and Innovation in Biomedicine, University of Rouen , Mont-Saint-Aignan, Rouen, France .
authors: Ifat
authors: I
authors: Alsharif
authors: 1 Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , Mont-Saint-Aignan, France .|2 Com UE, Normandy University of Rouen , France .|3 Institute for Research and Innovation in Biomedicine, University of Rouen , Mont-Saint-Aignan, Rouen, France .
authors: Matthieu
authors: M
authors: Castex
authors: 4 Faculty of Sciences, University of Rouen , Mont-Saint-Aignan, France.
authors: Arnaud
authors: A
authors: Arabo
authors: 1 Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , Mont-Saint-Aignan, France .|2 Com UE, Normandy University of Rouen , France .|3 Institute for Research and Innovation in Biomedicine, University of Rouen , Mont-Saint-Aignan, Rouen, France .
authors: Sana
authors: S
authors: El Hajji
authors: 1 Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , Mont-Saint-Aignan, France .|2 Com UE, Normandy University of Rouen , France .|3 Institute for Research and Innovation in Biomedicine, University of Rouen , Mont-Saint-Aignan, Rouen, France .
authors: Jean-Jacques
authors: JJ
authors: Bonnet
authors: 5 Department of Biology, Faculty of Sciences, Abdelmalek Essaadi University , Tetouan, Morocco .
authors: Mohammed
authors: M
authors: Errami
authors: 1 Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , Mont-Saint-Aignan, France .|2 Com UE, Normandy University of Rouen , France .|3 Institute for Research and Innovation in Biomedicine, University of Rouen , Mont-Saint-Aignan, Rouen, France .
authors: Anthony
authors: A
authors: Falluel-Morel
authors: 1 Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , Mont-Saint-Aignan, France .|2 Com UE, Normandy University of Rouen , France .|3 Institute for Research and Innovation in Biomedicine, University of Rouen , Mont-Saint-Aignan, Rouen, France .
authors: Abdeslam
authors: A
authors: Chagraoui
authors: 1 Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , Mont-Saint-Aignan, France .|2 Com UE, Normandy University of Rouen , France .|3 Institute for Research and Innovation in Biomedicine, University of Rouen , Mont-Saint-Aignan, Rouen, France .
authors: Isabelle
authors: I
authors: Lihrmann
authors: 1 Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , Mont-Saint-Aignan, France .|2 Com UE, Normandy University of Rouen , France .|3 Institute for Research and Innovation in Biomedicine, University of Rouen , Mont-Saint-Aignan, Rouen, France .
authors: Youssef
authors: Y
authors: Anouar
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009498:Neurotoxins / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D051140:Selenoproteins / Q000172:deficiency / Q000378:metabolism*
chemical_list: D009498:Neurotoxins; D051140:Selenoproteins; C547431:selenoprotein T, mouse; D010088:Oxidoreductases