Webbläsaren som du använder stöds inte av denna webbplats. Alla versioner av Internet Explorer stöds inte längre, av oss eller Microsoft (läs mer här: * https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Var god och använd en modern webbläsare för att ta del av denna webbplats, som t.ex. nyaste versioner av Edge, Chrome, Firefox eller Safari osv.

Selective neuroprotective effects of the S18Y polymorphic variant of UCH-L1 in the dopaminergic system

In English

Författare

  • Maria Xilouri
  • Elli Kyratzi
  • Pothitos M. Pitychoutis
  • Zoi Papadopoulou-Daifoti
  • Celine Perier
  • Miquel Vila
  • Matina Maniati
  • Ayse Ulusoy
  • Deniz Kirik
  • David S. Park
  • Keiji Wada
  • Leonidas Stefanis
Visa allt

Summary, in English

Genetic studies have implicated the neuronal ubiquitin C-terminal hydrolase (UCH) protein UCH-L1 in Parkinson's disease (PD) pathogenesis. Moreover, the function of UCH-L1 may be lost in the brains of PD and Alzheimer's disease patients. We have previously reported that the UCH-L1 polymorphic variant S18Y, potentially protective against PD in population studies, demonstrates specific antioxidant functions in cell culture. Albeit genetic, biochemical and neuropathological data support an association between UCH-L1, PD, synaptic degeneration and oxidative stress, the relationship between the dopaminergic system and UCH-L1 status remains obscure. In the current study, we have examined the dopaminergic system of mice lacking endogenous UCH-L1 protein (gracile axonal dystrophy mice). Our findings show that the lack of wild-type (WT) UCH-L1 does not influence to any significant degree the dopaminergic system at baseline or following injections of the neurotoxin methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Furthermore, using a novel intrastriatal adenoviral injection protocol, we have found that mouse nigral neurons retrogradely transduced with S18Y UCH-L1, but not the WT protein, are significantly protected against MPTP toxicity. Overall, these data provide evidence for an antioxidant and neuroprotective effect of the S18Y variant of UCH-L1, but not of the WT protein, in the dopaminergic system, and may have implications for the pathogenesis of PD or related neurodegenerative conditions, in which oxidative stress might play a role.

Publiceringsår

2012

Språk

Engelska

Sidor

874-889

Publikation/Tidskrift/Serie

Human Molecular Genetics

Volym

21

Issue

4

Dokumenttyp

Artikel i tidskrift

Förlag

Oxford University Press

Ämne

  • Medical Genetics

Status

Published

Forskningsgrupp

  • Brain Repair and Imaging in Neural Systems (BRAINS)

ISBN/ISSN/Övrigt

  • ISSN: 0964-6906