Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta no. 364, Casilla 114-D, 8330024 Santiago, Chile.
Oxid Med Cell Longev. 2012;2012:205713. doi: 10.1155/2012/205713. Epub 2012 Jun 5.
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.
尼曼-匹克 C 型（NPC）病是一种神经内脏非典型脂质贮积病，涉及胆固醇和其他脂质在内体晚期途径中的积累。目前尚不清楚 NPC 病中中枢神经系统和肝脏中细胞内胆固醇积累与细胞死亡之间的致病机制。在 NPC 小鼠的肝脏和大脑以及不同的 NPC 细胞模型中都观察到氧化应激。此外，有证据表明 NPC 患者的血清中氧化应激标志物升高。最近的证据强烈表明，线粒体功能障碍在 NPC 的发病机制中起着重要作用，并且线粒体可能是这种疾病中氧化应激的重要来源。在这种情况下，NPC 中晚期内体/溶酶体隔室中维生素 E 的积累可能导致其生物利用度降低，这可能是氧化损伤的另一个潜在原因。NPC 中另一个活性氧物质的可能来源是不同抗氧化酶活性的降低。此外，由于 NPC 主要是由游离胆固醇的积累引起的，因此氧化应激产生的氧化胆固醇衍生物可能有助于疾病的发病机制。
