Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy.
Cell Death Differ
; 22(11): 1742-53, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-25822341
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estilbenos
/
Adrenoleucodistrofia
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Sirtuína 1
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article