Clausen J
Acta Neurol Scand. 1984 Nov;70(5):345-55. doi: 10.1111/j.1600-0404.1984.tb00835.x.
The present communication surveys the present knowledge about the extent to which formation of free radicals in the central nervous system may give rise to cross-linking reactions finally ending in the deposition of lipofuscin pigments. Free radicals may be formed by autoperoxidation of polyunsaturated fatty acids. These fatty acids, e.g., C22:6 omega 3, are enriched in rods and cones of the eye and in phosphatidyl ethanolamine of synaptosomes. By peroxidation, malondialdehyde is formed. This aldehyde may cross-link through amino groups of proteins and certain phospholipids. Hereby, lipofuscin is deposited. The peroxidation process is counteracted by certain enzymic systems and by antioxidants. Thus, glutathionperoxidase (GSH-Px), catalase and superoxid dismutase may eliminate peroxides. GSH-Px is a selenium-containing enzyme. Peroxides are also formed by metabolic transformation of dopamine. 3 demential syndromes, i.e. Alzheimer's, Parkinson's and Batten's diseases, are discussed with regard to whether the "free radical theory" may explain the pathogenesis. Finally, it is discussed whether an antioxidative treatment including vitamins E and C as well as a supplement of selenium, e.g. sodiumselenite, may be a therapeutic alternative to other types of treatment of demential syndromes or a direct supplement to the L-DOPA treatment of Parkinson's disease.
本通讯综述了目前关于中枢神经系统中自由基形成在多大程度上可能引发交联反应并最终导致脂褐素沉积的知识。自由基可由多不饱和脂肪酸的自动氧化形成。这些脂肪酸，例如二十二碳六烯酸（C22:6 ω3），在眼睛的视杆细胞和视锥细胞以及突触体的磷脂酰乙醇胺中含量丰富。通过过氧化作用会形成丙二醛。这种醛可能会通过蛋白质和某些磷脂的氨基发生交联。由此，脂褐素得以沉积。过氧化过程会受到某些酶系统和抗氧化剂的抑制。因此，谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢酶和超氧化物歧化酶可以清除过氧化物。GSH-Px是一种含硒酶。多巴胺的代谢转化也会形成过氧化物。针对阿尔茨海默病、帕金森病和巴顿病这三种痴呆综合征，讨论了“自由基理论”是否可以解释其发病机制。最后，探讨了包括维生素E和C以及补充硒（如亚硒酸钠）在内的抗氧化治疗是否可以作为痴呆综合征其他治疗类型的替代疗法，或者作为帕金森病左旋多巴治疗的直接补充。
