Energy deficit in Huntington disease

why it matters

Mochel, Fanny
Haller, Ronald G.

¹INSERM UMR S975, Institut du Cerveau et de la Moelle, ²AP-HP, Département de Génétique, and ³Unité Fonctionnelle Neurométabolique, Hôpital La Salpêtrière, Paris, France. ⁴Université Pierre et Marie Curie, Paris, France. ⁵Department of Neurology, University of Texas Southwestern Medical Center and VA North Texas Medical Center, Dallas, Texas, USA. ⁶Neuromuscular Center, Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas, Texas, USA.

Address correspondence to: Ronald G. Haller, Department of Neurology, VA Medical Center and University of Texas Southwestern Medical Center and Neuromuscular Center, Institute for Exercise and Environmental Medicine of Presbyterian Hospital, Dallas, Texas 75231, USA. Phone: 214.345.4617; Fax: 214.345.4618; E-mail: [email protected].

Journal of Clinical Investigation 121(2):p 493-499, February 1, 2011. | DOI: 10.1172/JCI45691

Huntington disease (HD) is an autosomal dominant neurodegenerative disease with complete penetrance. Although the understanding of the cellular mechanisms that drive neurodegeneration in HD and account for the characteristic pattern of neuronal vulnerability is incomplete, defects in energy metabolism, particularly mitochondrial function, represent a common thread in studies of HD pathogenesis in humans and animal models. Here we review the clinical, biochemical, and molecular evidence of an energy deficit in HD and discuss the mechanisms underlying mitochondrial and related alterations.