Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's disease.
Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the IT-15 gene; however, it remains unknown how the mutation leads to selective neurodegeneration. Several lines of evidence suggest impaired mitochondrial function as a component of the neurodegenerative process in HD. We assessed energy metabolism in the skeletal muscle of 15 HD patients and 12 asymptomatic mutation carriers in vivo using 31P magnetic resonance spectroscopy. Phosphocreatine recovery after exercise is a direct measure of ATP synthesis and was slowed significantly in HD patients and mutation carriers in comparison to age- and gender-matched healthy controls. We found that oxidative function is impaired to a similar extent in manifest HD patients and asymptomatic mutation carriers. Our findings suggest that mitochondrial dysfunction is an early and persistent component of the pathophysiology of HD.
Saft
Carsten
C
Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Germany.
Zange
Jochen
J
Andrich
Jürgen
J
Müller
Klaus
K
Lindenberg
Katrin
K
Landwehrmeyer
Bernhard
B
Vorgerd
Matthias
M
Kraus
Peter H
PH
Przuntek
Horst
H
Schöls
Ludger
L
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D004734:Energy Metabolism / Q000502:physiology; D015444:Exercise / Q000502:physiology; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D007150:Immunohistochemistry / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D018482:Muscle, Skeletal / Q000503:physiopathology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D011930:Reaction Time / Q000502:physiology
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010725:Phosphocreatine; D000255:Adenosine Triphosphate