Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy.

Abstract

Oxidative stress and mitochondrial failure are prominent factors in the axonal degeneration process. In this study, we demonstrate that sirtuin 1 (SIRT1), a key regulator of the mitochondrial function, is impaired in the axonopathy and peroxisomal disease X-linked adrenoleukodystrophy (X-ALD). We have restored SIRT1 activity using a dual strategy of resveratrol treatment or by the moderate transgenic overexpression of SIRT1 in a X-ALD mouse model. Both strategies normalized redox homeostasis, mitochondrial respiration, bioenergetic failure, axonal degeneration and associated locomotor disabilities in the X-ALD mice. These results indicate that the reactivation of SIRT1 may be a valuable strategy to treat X-ALD and other axonopathies in which the control of redox and energetic homeostasis is impaired.

• Authors: L Morató, M Ruiz, J Boada, N Y Calingasan, J Galino, C Guilera, M Jové, A Naudí, I Ferrer, R Pamplona, M Serrano, M Portero-Otín, M F Beal, S Fourcade, A Pujol
• Journal: Cell death and differentiation (Cell Death Differ) Vol. 22 Issue 11 Pg. 1742-53 (Nov 2015) ISSN: 1476-5403 [Electronic] England
• PMID: 25822341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Stilbenes
• Sirtuin 1
• Resveratrol

Topics

• Adrenoleukodystrophy (drug therapy, genetics, metabolism, therapy)
• Animals
• Blotting, Western
• Disease Models, Animal
• Humans
• In Vitro Techniques
• Locomotion (drug effects, genetics)
• Mice
• Mice, Mutant Strains
• Oxidation-Reduction
• Real-Time Polymerase Chain Reaction
• Resveratrol
• Sirtuin 1 (genetics, metabolism)
• Stilbenes (therapeutic use)