神经退化性疾病生物能量代谢和氧化应激研究进展

衰老是导致几种常见的神经系统退化性疾病的主要危险因素，包括帕金森氏病（Ｐａｒｋｉｎｓｏｎ’ｓ ｄｉｓｅａｓｅ ＰＤ），肌萎缩性侧索硬化（Ａｍｙｏｔｒｏｐｈｉｃ ｌａｔｅｒａｌ ｓｃｌｅｒｏｓｉｓ，ＡＬＳ），早老性痴呆（Ａｌｚｈｅｉｍｅｒ’ｓ ｄｉｓｅａｓｅ ＡＤ）和亨廷顿氏病（Ｈｕｎｔｉｎｇｔｏｎ’ｓ ｄｉｓｅａｓｅ ＨＤ）。最近研究表明，神经退化性疾病涉及到线粒体缺陷，氧化应激等因素。在脑和其它组织中，老化可导致线粒体功能的损伤和氧化损伤的增强。ＰＤ病人中，已发现线粒体复合酶体Ⅰ活性降低，氧化损伤增加和抗氧化系统活性的改变。在几例家族性ＡＬＳ病人中，也发现Ｃｕ、Ｚｎ超氧化物歧化酶（Ｃｕ，Ｚｎ ＳＯＤ）基因的突变，导致Ｃｕ、Ｚｎ超氧化物歧化酶活性减低；散发的ＡＬＳ病人氧化损伤增高。在ＨＤ病人中已发现能量代谢异常

Bioenergetic and Oxidative Stress in Neuro degenerative Diseases

Aging is a major risk factor for several common neurodegenerative diseases, including Parkinson's disease(PD), amyotrophic lateral sclerosis(ALS), Alzheimer's disease(AD), and Hunting'sdisease(HD). Recent studies have implicated mitochondrial dysfunction and oxidative stress in the aging process and also in pathogenetic neurodegenerative diseases. In brain and other tissues, aging is associated with progressive impairment of mitochondrial fuction and increase of oxidative damage. In PD, several studies have demonstrated decreased complex I activity, increased oxidative damage, and the changed activities of antioxidant defense systems. Some cases of familial HD are associated with mutations in the gene for Cu, Zn superoxide dismutase(Cu, Zn SOD) and decreased Cu, Zn SOD activity, while sporadic ALS oxidative damage may be increased. Defects in energy metabolism and increased cortical lacte levels have been detected in HD patients. Studies of AD patients have identified decreased complex IV activity, and some patients with AD and PD have mitochondrial DNA mutations. The age related onset and progressive course of these neurodegenerative diseases may be due to a cycle process between impaired energy metabolism and oxidative stresses.