Kimura T, Takamatsu J, Miyata T, Miyakawa T, Horiuchi S
Department of Neuropsychiatry, Kumamoto University School of Medicine, Japan.
Pathol Int. 1998 Aug;48(8):575-9. doi: 10.1111/j.1440-1827.1998.tb03953.x.
The recent identification of age-related accumulation of advanced glycation end-products (AGE) of the Maillard reaction in neurons and vessels of the human brain suggests the involvement of AGE in the aging process. A variety of inclusions such as lipofuscin granules, corpora amylacea, Hirano bodies, granulovacuolar degenerations and ubiquitin-positive granular structures are found in the aged human brain. These age-related inclusions contain insoluble and non-degradable proteins. Advanced glycation end-product-modified proteins are also known to be insoluble and protease resistant. The similarity between proteins in such inclusions and AGE-modified proteins suggests the presence of AGE in inclusions. To investigate this possibility, the presence of two known AGE structures, N epsilon(carboxymethyl)lysine (CML) and pentosidine, was examined in age-related inclusions. Immunohistochemical examination of the medial temporal area of brain tissues obtained at autopsy from seven non-demented elderly individuals demonstrated positive reactions in lipofuscin granules and corpora amylacea but not in other inclusions for anti-CML and anti-pentosidine antibodies. As CML and pentosidine are glycoxidation products among AGE, the results suggest that glycation and/or oxidation may be involved in the formation of lipofuscin granules and corpora amylacea.
最近在人类大脑的神经元和血管中发现了与年龄相关的美拉德反应晚期糖基化终产物（AGE）的积累，这表明AGE参与了衰老过程。在老年人脑中发现了多种内含物，如脂褐素颗粒、淀粉样体、 Hirano小体、颗粒空泡变性和泛素阳性颗粒结构。这些与年龄相关的内含物含有不溶性且不可降解的蛋白质。已知晚期糖基化终产物修饰的蛋白质也是不溶性的且具有蛋白酶抗性。此类内含物中的蛋白质与AGE修饰蛋白质之间的相似性表明内含物中存在AGE。为了研究这种可能性，在与年龄相关的内含物中检测了两种已知的AGE结构，即Nε-（羧甲基）赖氨酸（CML）和戊糖苷。对7名非痴呆老年人尸检获得的脑组织颞叶内侧区域进行免疫组织化学检查，结果显示抗CML和抗戊糖苷抗体在脂褐素颗粒和淀粉样体中呈阳性反应，而在其他内含物中则无阳性反应。由于CML和戊糖苷是AGE中的糖氧化产物，结果表明糖基化和/或氧化可能参与了脂褐素颗粒和淀粉样体的形成。
