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[脂质代谢在阿尔茨海默病中的作用]

[The role of lipid metabolism in Alzheimer's disease].

作者信息

Kamino Kouzin, Tanaka Toshihisa, Kida Tomoyuki, Ohkochi Masayasu, Tanii Hisashi, Kudo Takashi, Takeda Masatoshi

机构信息

Division of Psychiatry and Behavioral Proteomics, Department of Post-Genomics and Diseases, Osaka University Graduate School of Medicine, 2-2, D3, Yamadaoka, Suita, 565-0871 Japan.

出版信息

Nihon Shinkei Seishin Yakurigaku Zasshi. 2002 Aug;22(4):103-10.

Abstract

Lipid metabolism in the central nervous system has been focused as an important factor of Alzheimer's disease, since the apolipoprotein E gene was discovered as a genetic risk for the disease. Lipid metabolism in the brain, showing relatively closed environment, necessitates lipid reutilization. Cerebrospinal fluid contains only high-density lipoproteins composed of apoE and apoJ secreted from astrocytes and of apoA-I and apoA-II transported via the blood brain barrier. These apolipoproteins can bind to beta amyloid and possibly relate to its clearance. The aggregation of phosphorylated tau, found in neurofibrillary tangles in Alzheimer's brain, is also found in the brain with Niemann-Pick disease, suggesting that the impairment of lipid transport in neuronal cells participates in Alzheimer's disease. Mitochondrial function, lipid production, and acetylcholine production are closely related, and these alterations could be involved in cholinergic dysfunction in Alzheimer's disease. The regulation of lipid metabolism in and outside the brain could be a therapeutic and preventive target for Alzheimer's disease.

摘要

自载脂蛋白E基因被发现是阿尔茨海默病的遗传风险因素以来,中枢神经系统中的脂质代谢一直被视为该病的一个重要因素。大脑中的脂质代谢处于相对封闭的环境,需要脂质再利用。脑脊液仅包含由星形胶质细胞分泌的载脂蛋白E和载脂蛋白J以及通过血脑屏障转运的载脂蛋白A-I和载脂蛋白A-II组成的高密度脂蛋白。这些载脂蛋白可以与β淀粉样蛋白结合,并可能与其清除有关。在阿尔茨海默病大脑的神经原纤维缠结中发现的磷酸化tau蛋白聚集,在患有尼曼-匹克病的大脑中也有发现,这表明神经元细胞中脂质转运的受损参与了阿尔茨海默病。线粒体功能、脂质生成和乙酰胆碱生成密切相关,这些改变可能与阿尔茨海默病中的胆碱能功能障碍有关。大脑内外脂质代谢的调节可能是阿尔茨海默病的治疗和预防靶点。

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