No evidence for substrate accumulation in Parkinson brains with GBA mutations.
No evidence for substrate accumulation in Parkinson brains with GBA mutations.
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DOI：
10.1002/mds.26278
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Schapira AH
中科院分区：
文献类型：
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作者：
Gegg ME;Sweet L;Wang BH;Shihabuddin LS;Sardi SP;Schapira AH
确定先前描述的葡萄糖脑苷脂酶活性降低的帕金森病（PD）脑是否表现出溶酶体酶底物葡萄糖神经酰胺的蓄积或脂质组成的其他变化。对对照组、GBA 1杂合子突变（PD+GBA）帕金森病脑或散发性PD的壳核（n = 5 - 7）和小脑（n = 7 - 14）进行脂质组学分析和胆固醇测量。与对照组相比，PD+GBA和散发性PD脑中的总葡萄糖神经酰胺水平无变化。在壳核或小脑中未观察到葡萄糖鞘氨醇（脱乙酰葡萄糖神经酰胺）、鞘磷脂、神经节苷脂（GM 2、GM 3）或总胆固醇的变化。本研究未证明在具有低α-突触核蛋白病理学的脑区域中具有杂合子GBA 1突变的PD脑中葡萄糖脑苷脂酶底物蓄积。版权所有© 2015作者.出版社：Wiley Periodicals，Inc.国际帕金森和运动障碍协会（International Parkinson and Movement Disorder Society）
To establish whether Parkinson's disease (PD) brains previously described to have decreased glucocerebrosidase activity exhibit accumulation of the lysosomal enzyme's substrate, glucosylceramide, or other changes in lipid composition. Lipidomic analyses and cholesterol measurements were performed on the putamen (n = 5‐7) and cerebellum (n = 7‐14) of controls, Parkinson's disease brains with heterozygote GBA1 mutations (PD+GBA), or sporadic PD. Total glucosylceramide levels were unchanged in both PD+GBA and sporadic PD brains when compared with controls. No changes in glucosylsphingosine (deacetylated glucosylceramide), sphingomyelin, gangliosides (GM2, GM3), or total cholesterol were observed in either putamen or cerebellum. This study did not demonstrate glucocerebrosidase substrate accumulation in PD brains with heterozygote GBA1 mutations in areas of the brain with low α‐synuclein pathology. © 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.