Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy
Calingasan, Noel Ylagan
Beal, M. F.
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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.
Is part ofCell Death and Differentiation, 2015, vol. 22, p. 1742-1753
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Impaired mitochondrial oxidative phosphorylation in the peroxisomal disease X-linked adrenoleukodystrophy López Erauskin, Jone; Galino, Jorge; Ruiz, M.; Cuezva, J. M.; Fabregat, I.; Cacabelos Barral, Daniel; Boada Pallàs, Jordi; Martínez, Juan José; Ferrer, Isidre; Pamplona Gras, Reinald; Villarroya, Francesc; Portero Otín, Manuel; Fourcade, Stéphane; Pujol, A. (Oxford Journals, 2013)X-linked adrenoleukodystrophy (X-ALD) is an inherited metabolic disorder of the nervous system characterized by axonopathy in spinal cords and/or cerebral demyelination, adrenal insufficiency and accumulation of very ...
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