Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy

作者：Morato L; Ruiz M; Boada J; Calingasan N Y; Galino J; Guilera C; Jove M; Naudi A; Ferrer I; Pamplona R; Serrano M; Portero Otin M; Beal M F; Fourcade S; Pujol A^*

来源：Cell Death and Differentiation, 2015, 22(11): 1742-1753.

DOI：10.1038/cdd.2015.20

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.

• 出版日期2015-11