Oxidative stress and plasma aminopeptidase activity in Huntington's disease.
Huntington's disease (HD) is a genetic neurodegenerative disorder. Oxidative stress, mitochondrial dysfunction, and protein metabolism impairment have been implicated in its pathogenesis. However, the contribution of these phenomena to HD onset or progression is not well known, and they have been less studied in peripheral blood. We analyzed plasma lipid peroxide (LPO) and lactate (LAC) concentrations as indicators of oxidative stress and mitochondrial dysfunction in symptomatic HD patients (sHD) and asymptomatic HD gene carriers (aHD). We also measured the plasma activity of aminopeptidases (APs), an important group of proteolytic enzymes. LPO and LAC concentrations were significantly elevated in sHD patients but not in aHD carriers. Aspartate and glutamate AP activities were significantly reduced in sHD patients and aHD carriers. These findings demonstrate that sHD patients are under oxidative stress, which may favor progression of the disease. Plasma AP activity was decreased before the appearance of HD symptoms and oxidative stress and may be related to protein metabolism impairment. These results indicate that therapy directed to improve oxidative stress and normalize AP activity may be useful in the treatment of HD. They also suggest that decreased plasma AP activity in aHD carriers may predict the future onset of HD symptoms.
Duran
Raquel
R
Department of Physiology, University of Granada, Granada, Spain.
Barrero
Francisco J
FJ
Morales
Blas
B
Luna
Juan D
JD
Ramirez
Manuel
M
Vives
Francisco
F
D000328:Adult; D000626:Aminopeptidases / Q000097:blood*; D005260:Female; D006579:Heterozygote; D006801:Humans; D006816:Huntington Disease / Q000097:blood* / Q000201:enzymology / Q000235:genetics; D019344:Lactic Acid / Q000097:blood*; D008054:Lipid Peroxides / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
D008054:Lipid Peroxides; D019344:Lactic Acid; D000626:Aminopeptidases