Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
Neurochem Res. 2011 Sep;36(9):1578-86. doi: 10.1007/s11064-011-0494-2. Epub 2011 May 12.
A number of studies have suggested functions of sialic acid-containing glycosphingolipids (gangliosides) in the nervous system. However, results of analyses of the mutant mice lacking gangliosides suggested that they play crucial roles in the maintenance of integrity and repair of the nervous tissues. Furthermore, results of double knockout mice lacking all gangliosides except GM3 (GM3-only mice) suggested that deficiency of gangliosides induced complement activation and inflammation, leading to neurodegeneration. Generation of triple knockout mice by mating GM3-only mice and C3-deficient mice verified the involvement of complement systems in the inflammation and neurodegeneration. For the mechanisms of the complement activation, functional disorders of complement-regulatory proteins such as CD55 and CD59, which belong to GPI-anchored proteins, should be main factors. These results suggested that normal composition of gangliosides is essential for the maintenance of lipid rafts. Therefore, it was suggested that regulation of the complement systems and suppression of the inflammation should be important for the treatment of neurodegeneration, having common aspects with other neurodegenerative diseases such as Alzheimer disease.
已有多项研究表明唾液酸糖脂（神经节苷脂）在神经系统中的功能。然而，对缺乏神经节苷脂的突变体小鼠的分析结果表明，它们在维持神经组织的完整性和修复中起着至关重要的作用。此外，缺乏除 GM3 以外所有神经节苷脂的双敲除小鼠（仅 GM3 敲除小鼠）的结果表明，神经节苷脂的缺乏诱导补体激活和炎症，导致神经退行性变。通过将仅 GM3 敲除小鼠与 C3 缺陷小鼠交配产生的三重敲除小鼠证实了补体系统在炎症和神经退行性变中的参与。对于补体激活的机制，属于 GPI 锚定蛋白的补体调节蛋白（如 CD55 和 CD59）的功能障碍可能是主要因素。这些结果表明，神经节苷脂的正常组成对于脂筏的维持是必要的。因此，调节补体系统和抑制炎症对于神经退行性变的治疗应该是重要的，这与阿尔茨海默病等其他神经退行性疾病具有共同的方面。
