Baek Rena C, Martin Douglas R, Cox Nancy R, Seyfried Thomas N
Biology Department, Boston College, Chestnut Hill, MA 02467, USA.
Lipids. 2009 Mar;44(3):197-205. doi: 10.1007/s11745-008-3268-0. Epub 2008 Nov 26.
Sandhoff disease (SD) is a glycosphingolipid (GSL) storage disease that arises from an autosomal recessive mutation in the gene for the beta-subunit of beta-Hexosaminidase A (Hexb gene), which catabolizes ganglioside GM2 within lysosomes. Accumulation of GM2 and asialo-GM2 (GA2) occurs primarily in the CNS, leading to neurodegeneration and brain dysfunction. We analyzed the total lipids in the brains of SD mice, cats, and humans. GM2 and GA2 were mostly undetectable in the normal mouse, cat, and human brain. The lipid abnormalities in the SD cat brain were generally intermediate to those observed in the SD mouse and the SD human brains. GM2 comprised 38, 67, and 87% of the total brain ganglioside distribution in the SD mice, cats, and humans, respectively. The ratio of GA2-GM2 was 0.93, 0.13, and 0.27 in the SD mice, cats, and humans, respectively, suggesting that the relative storage of GA2 is greater in the SD mouse than in the SD cat or human. Finally, the myelin-enriched lipids, cerebrosides and sulfatides, were significantly lower in the SD brains than in the control brains. This study is the first comparative analysis of brain lipids in mice, cats, and humans with SD and will be important for designing therapies for Sandhoff disease patients.
桑德霍夫病（SD）是一种糖鞘脂（GSL）贮积病，由β-氨基己糖苷酶A的β亚基基因（Hexb基因）的常染色体隐性突变引起，该酶在溶酶体内分解神经节苷脂GM2。GM2和脱唾液酸GM2（GA2）的蓄积主要发生在中枢神经系统，导致神经退行性变和脑功能障碍。我们分析了SD小鼠、猫和人类大脑中的总脂质。在正常小鼠、猫和人类大脑中，GM2和GA2大多检测不到。SD猫脑的脂质异常通常介于SD小鼠和SD人类大脑所观察到的异常之间。GM2分别占SD小鼠、猫和人类大脑神经节苷脂总分布的38%、67%和87%。SD小鼠、猫和人类中GA2与GM2的比例分别为0.93、0.13和0.27，这表明SD小鼠中GA2的相对蓄积量比SD猫或人类中的更大。最后，富含髓磷脂的脂质、脑苷脂和硫脂在SD大脑中显著低于对照大脑。本研究是首次对患有SD的小鼠、猫和人类的脑脂质进行比较分析，对设计针对桑德霍夫病患者的治疗方法具有重要意义。
