Oxidative stress: a pathogenic mechanism for Niemann-Pick type C disease.
Niemann-Pick type C (NPC) disease is a neurovisceral atypical lipid storage disorder involving the accumulation of cholesterol and other lipids in the late endocytic pathway. The pathogenic mechanism that links the accumulation of intracellular cholesterol with cell death in NPC disease in both the CNS and the liver is currently unknown. Oxidative stress has been observed in the livers and brains of NPC mice and in different NPC cellular models. Moreover, there is evidence of an elevation of oxidative stress markers in the serum of NPC patients. Recent evidence strongly suggests that mitochondrial dysfunction plays an important role in NPC pathogenesis and that mitochondria could be a significant source of oxidative stress in this disease. In this context, the accumulation of vitamin E in the late endosomal/lysosomal compartments in NPC could lead to a potential decrease of its bioavailability and could be another possible cause of oxidative damage. Another possible source of reactive species in NPC is the diminished activity of different antioxidant enzymes. Moreover, because NPC is mainly caused by the accumulation of free cholesterol, oxidized cholesterol derivatives produced by oxidative stress may contribute to the pathogenesis of the disease.
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta no. 364, Casilla 114-D, 8330024 Santiago, Chile.
Mary Carmen
MC
Vázquez
Elisa
E
Balboa
Alejandra R
AR
Alvarez
Silvana
S
Zanlungo
D000818:Animals; D001921:Brain / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D006028:Glycosphingolipids / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D052556:Niemann-Pick Disease, Type C / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D020675:Peroxisomes / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
D006028:Glycosphingolipids; D011506:Proteins; C018589:lysosomal proteins; D014810:Vitamin E; D002784:Cholesterol