Comparative analysis of brain lipids in mice, cats, and humans with Sandhoff disease.
Comparative analysis of brain lipids in mice, cats, and humans with Sandhoff disease.
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DOI：
10.1007/s11745-008-3268-0
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发表时间：
2009-03
期刊：
影响因子：
1.9
通讯作者：
Seyfried, Thomas N.
中科院分区：
文献类型：
--
作者：
Baek, Rena C.;Martin, Douglas R.;Cox, Nancy R.;Seyfried, Thomas N.
关键词：
桑德霍夫病（SD）是一种糖鞘脂（GSL）贮积症，由β -己糖胺酶A的β -亚基基因（Hexb基因）发生常染色体隐性突变引起，该酶在溶酶体内分解代谢神经节苷脂GM2。GM2和无唾液酸 - GM2（GA2）主要在中枢神经系统积聚，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大多无法检测到。SD猫大脑中的脂质异常情况通常介于SD小鼠和SD人类大脑之间。在SD小鼠、猫和人类中，GM2分别占大脑神经节苷脂总分布的38%、67%和87%。在SD小鼠、猫和人类中，GA2与GM2的比率分别为0.93、0.13和0.27，这表明SD小鼠中GA2的相对贮积量比SD猫或人类更大。最后，富含髓鞘的脂质、脑苷脂和硫脂在SD大脑中的含量明显低于对照大脑。这项研究是对患有SD的小鼠、猫和人类大脑脂质的首次比较分析，对设计桑德霍夫病患者的治疗方法具有重要意义。
Sandhoff disease (SD) is a glycosphingolipid (GSL) storage disease that arises from an autosomal recessive mutation in the gene for the β-subunit of β-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 to 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.
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