Jenner P
Biomedical Sciences Division, King's College London, UK.
Pathol Biol (Paris). 1996 Jan;44(1):57-64.
The cause of cell death in neurodegenerative diseases remains unknown but the formation of free radicals and the occurrence of oxidative stress may be a common component of many, if not all, such disorders. For example, in substantia nigra in Parkinson's diseases key alterations occur, in iron handling, mitochondrial function and antioxidant defences, particularly reduced glutathione. These indices of oxidative stress are accompanied by evidence of free radical mediated damage in the form of increased lipid peroxidation and oxidation of DNA bases. The alterations in oxidative stress occurring in Parkinson's disease appear not be related to the administration of L-DOPA. Some alterations of oxidative stress are found in other basal ganglia in degenerative disorders (multiple system atrophy, progressive supranuclear palsy, Huntington's disease) but these have not been investigated to the same extent. Similarly, examination of biochemical changes occurring in Alzheimer's disease, motor neurone disease and diabetic neuropathy also suggest the involvement of free radical mediated mechanisms as a component of neurodegeneration. It is probable that irrespective of the primary cause of individual neurodegenerative disorder, the onset of oxidative stress is a common mechanism by which neuronal death occurs and which contributes to disease progression. Clearly, therapeutic strategies aimed at limiting free radical production and oxidative stress and/or damage may slow the advance of neurodegenerative disease.
神经退行性疾病中细胞死亡的原因尚不清楚,但自由基的形成和氧化应激的发生可能是许多(即便不是所有)此类疾病的共同因素。例如,在帕金森病的黑质中,铁代谢、线粒体功能和抗氧化防御,尤其是谷胱甘肽水平,会发生关键改变。这些氧化应激指标伴随着自由基介导损伤的证据,表现为脂质过氧化增加和DNA碱基氧化。帕金森病中发生的氧化应激改变似乎与左旋多巴的使用无关。在其他退行性疾病(多系统萎缩、进行性核上性麻痹、亨廷顿病)的基底神经节中也发现了一些氧化应激改变,但尚未进行同等程度的研究。同样,对阿尔茨海默病、运动神经元病和糖尿病性神经病变中发生的生化变化的研究也表明,自由基介导的机制参与了神经退行性变过程。很可能无论个体神经退行性疾病的主要病因是什么,氧化应激的发生都是神经元死亡的常见机制,并且会促进疾病进展。显然,旨在限制自由基产生、氧化应激和/或损伤的治疗策略可能会减缓神经退行性疾病的进展。