Universitat de Lleida
    • English
    • català
    • español
  • español 
    • English
    • català
    • español
  • Mi DSpace
Repositori Obert UdL
Ver ítem 
  •   DSpace Principal
  • Recerca
  • Medicina Experimental
  • Articles publicats (Medicina Experimental)
  • Ver ítem
  •   DSpace Principal
  • Recerca
  • Medicina Experimental
  • Articles publicats (Medicina Experimental)
  • Ver ítem
JavaScript is disabled for your browser. Some features of this site may not work without it.

Pioglitazone halts axonal degeneration in a mouse model of X-linked adrenoleukodystrophy

Thumbnail
Ver/Abrir
020176.pdf (984.7Kb)
Sol·licita una còpia
Fecha de publicación
2013
Autor/a
Morató, Laia
Galino, Jorge
Ruiz, Montserrat
Calingasan, Noel Ylagan
Starkov, Anatoly A.
Dumont, Magali
Naudí i Farré, Alba
Martínez, Juan José
Aubourg, Patrick
Portero Otín, Manuel
Pamplona Gras, Reinald
Galea, Elena
Flint Beal, M.
Ferrer, Isidre
Fourcade, Stéphane
Pujol, Aurora
Impacto


Logo de Web of Science    citaciones en Web of Science

Logo de Scopus    citaciones en Scopus

Logo de Google Académico  Google Académico
Compartir
Exportar a Mendeley
Metadatos
Mostrar el registro completo del ítem
Resumen
X-linked adrenoleukodystrophy is a neurometabolic disorder caused by inactivation of the peroxisomal ABCD1 transporter of very long-chain fatty acids. In mice, ABCD1 loss causes late onset axonal degeneration in the spinal cord in association with locomotor disability resembling the most common phenotype
in patients, adrenomyeloneuropathy. Increasing evidence indicates that oxidative stress and bioenergetic failure play major roles in the pathogenesis of X-linked adrenoleukodystrophy. In this study, we aimed to evaluate whether mitochondrial biogenesis is affected in X-linked adrenoleukodystrophy. We demonstrated that Abcd1 null mice show reduced mitochondrial DNA concomitant with downregulation of mitochondrial biogenesis pathway driven by PGC-1α/PPARγ and reduced expression of mitochondrial proteins cytochrome c, NDUFB8 and VDAC. Moreover, we show that the oral administration of pioglitazone, an agonist of PPARγ, restored mitochondrial content and expression of master regulators of biogenesis, neutralized oxidative damage to proteins and DNA, and reversed bioenergetic failure in terms of ATP levels, NAD+/NADH ratios, pyruvate kinase and glutathione reductase activities. Most importantly, the treatment halted locomotor disability and axonal damage in X-linked adrenoleukodystrophy mice. These results lend support to the use of pioglitazone in clinical trials with patients with adrenomyeloneuropathy and reveal novel molecular mechanisms of action of pioglitazone in neurodegeneration. Future studies should address the effects of this anti-diabetic drug on other axonopathies in which oxidative stress and mitochondrial dysfunction are contributing factors.
URI
http://hdl.handle.net/10459.1/58503
DOI
https://doi.org/10.1093/brain/awt143
Es parte de
Brain: a journal of neurology, 2013, vol. 136, núm. 8, p. 2432-2443
Colecciones
  • Articles publicats (IRBLleida) [599]
  • Publicacions de projectes de recerca del Plan Nacional [1762]
  • Publicacions de projectes finançats per la Unió Europea [430]
  • Articles publicats (Medicina Experimental) [204]
  • Articles publicats (Grup de Recerca en Fisiopatologia Metabòlica) [57]

Contacto | Sugerencias | Aviso legal
© 2019 BiD. Universitat de Lleida
Metadades subjectes a
 

 

Listar

Todo DSpaceComunidades y coleccionesPor fecha de publicaciónAutoresTítulosMateriasEsta colecciónPor fecha de publicaciónAutoresTítulosMaterias

Estadísticas

Ver Estadísticas de uso

D'interès

Política institucional d'accés obertDiposita les teves publicacionsDiposita dades de recercaSuport a la recerca

Contacto | Sugerencias | Aviso legal
© 2019 BiD. Universitat de Lleida
Metadades subjectes a