Van Dyke K
Department of Pharmacology & Toxicology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown 26506, USA.
Med Hypotheses. 1997 May;48(5):375-80. doi: 10.1016/s0306-9877(97)90031-1.
Alzheimer's disease is characterized by the development of a degenerative condition in the elderly, associated with dementia. Upon pathological examination, cerebral amyloid plaques are found which contain denatured protein or peptide material. The process of denaturation of protein requires the presence of excessive heat, organic solvents, or oxidizing acids (OA). It seems that only OA could produce these effects since the other two are not present in the disease. Macrophages can produce the anion of an oxidizing acid known as peroxynitrite (OONO). This material is formed from two free radical gases, namely superoxide anion [.O2]- and nitric oxide (.N = O). Although (OONO)- is very reactive (1000 times more oxidizing than hydrogen peroxide), its half life in solution is only 1 to 2 seconds. Therefore, when it oxidizes a substance (such as protein) peroxynitrite disappears. The brain contains cells called microglia which are produced from monocytes in the same way as other types of macrophages from the lung and liver etc. The macrophages from the lung (alveolar) and liver (Kupfer cells) produce large amounts of peroxynitrite when activated by particles (silica) or infectious agents (lipopolysaccharide or interferon). Microglia produce highly oxidizing substances as well, but no one has ever measured production of peroxynitrite from these cells. Assuming that microglia produce peroxynitrite, or other similar oxidants, anti-oxidant and anti-inflammatory drugs should be helpful in treatment of early forms of the disease. In addition, large doses of anti-oxidant vitamin C and vitamin E might be helpful to people with Alzheimer's disease.
阿尔茨海默病的特征是老年人出现一种与痴呆症相关的退行性病症。经病理检查，可发现含有变性蛋白质或肽物质的脑淀粉样斑块。蛋白质变性过程需要有过热、有机溶剂或氧化性酸（OA）存在。由于疾病中不存在其他两种因素，似乎只有OA能产生这些影响。巨噬细胞可产生一种名为过氧亚硝酸盐（OONO）的氧化性酸的阴离子。这种物质由两种自由基气体形成，即超氧阴离子[.O2]-和一氧化氮（.N = O）。尽管（OONO）-反应性很强（氧化性比过氧化氢高1000倍），但其在溶液中的半衰期仅为1至2秒。因此，当过氧亚硝酸盐氧化一种物质（如蛋白质）时就会消失。大脑中含有一种称为小胶质细胞的细胞，它与肺和肝脏等其他类型巨噬细胞一样由单核细胞产生。肺（肺泡）巨噬细胞和肝（枯否细胞）巨噬细胞在被颗粒（二氧化硅）或传染因子（脂多糖或干扰素）激活时会产生大量过氧亚硝酸盐。小胶质细胞也会产生强氧化性物质，但从未有人测量过这些细胞产生过氧亚硝酸盐的情况。假设小胶质细胞会产生过氧亚硝酸盐或其他类似的氧化剂，那么抗氧化和抗炎药物应该有助于治疗该疾病的早期形式。此外，大剂量的抗氧化维生素C和维生素E可能对阿尔茨海默病患者有益。
