戈谢氏病致病机制及治疗方法

doi:10.16288/j.yczz.14-459

遗传 ›› 2015, Vol. 37 ›› Issue (6): 510-516.doi: 10.16288/j.yczz.14-459

戈谢氏病致病机制及治疗方法

刘林玉¹, 杜司晨², 张进¹, 马端^{1, 2}

1.复旦大学代谢与分子医学教育部重点实验室,上海 200032;
2.复旦大学出生缺陷研究中心,上海 200032

收稿日期:2014-12-25 修回日期:2015-01-23 出版日期:2015-06-20 发布日期:2015-03-18
通讯作者: 马端,博士, 教授,研究方向：出生缺陷与血管性疾病的发病机制与干预策略。E-mail: duanma@fudan.edu.cn
作者简介:刘林玉,硕士研究生,专业方向：生物化学与分子生物学。E-mail: llynvxia@126.com 杜司晨,博士研究生,专业方向：医学系统生物学。E-mail: xiaodu1224@sina.com刘林玉和杜司晨并列第一作者。
基金资助:
国家自然科学基金项目(编号：81371269)和上海市科研计划项目(编号：14140902600)资助

Pathogenic mechanism and therapies for Gaucher’s disease

Linyu Liu¹, Sichen Du², Jin Zhang¹, Duan Ma^{1, 2}

1. The Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Fudan University, Shanghai 200032, China;
2. Research Center for Birth Defects, Fudan University, Shanghai 200032, China

Received:2014-12-25 Revised:2015-01-23 Online:2015-06-20 Published:2015-03-18

摘要/Abstract

摘要： 戈谢氏病(Gaucher's disease,GD)又称葡萄糖脑苷脂沉积病,是溶酶体贮积症(Lysosomal storage disorder)中最常见的一种,为常染色体隐性遗传病。此病因溶酶体中β-葡糖脑苷脂酶(β-glucocerebrosidase, GBA)编码基因异常,致使该酶活性降低,葡糖脑苷脂(Glucocerebroside, GlcCer)不能被水解而聚积在脑组织、肝脏、脾等组织的溶酶体及单核–巨噬系统中,导致细胞失去原有的功能而产生一系列症状：脑损伤、肝脾肿大、骨损害、血细胞减少、生长发育迟滞等。Ⅰ型GD以酶替代治疗(Enzyme replacement therapy, ERT)为主,但Ⅱ型和Ⅲ型无有效的治疗方法。文章对GD的致病机制及治疗方法的最新进展进行了综述。

关键词: 戈谢氏病, β, -葡萄糖脑苷脂酶, 致病机制, 酶替代治疗, 基因治疗

Abstract: Gaucher's disease (GD) also named glucocerebroside lipidosis, is the most common kind of 1ysosomal storage disorder. It results from an autosomal recessive deficiency of the lysosomal enzyme acid β-glucosidase/ β-glucocerebrosidase (GBA), which is responsible for hydrolysis of glucocerebroside/glucosylceramide (GlcCer) into glucose and ceramide. Absent or reduced enzymatic activity of GBA leads to multisystemic accumulation of GlcCer in mononuclear phagocyte system and various tissues, such as brain, liver, spleen and so on, causing brain injury, liver splenomegaly, bone damage, the reduction of blood cells and individual growth retardation. GD type I could be treated by enzyme replacement therapy (ERT), but GD types II and III have not effective treatment. In this review, we summarize the recent progress on pathogenic mechanism and therapies in GD.

Key words: Gaucher's disease, β, -glucocerebrosidase, pathogenic mechanism, enzyme replacement therapy, gene therapy

刘林玉, 杜司晨, 张进, 马端. 戈谢氏病致病机制及治疗方法[J]. 遗传, 2015, 37(6): 510-516.

Linyu Liu, Sichen Du, Jin Zhang, Duan Ma. Pathogenic mechanism and therapies for Gaucher’s disease[J]. HEREDITAS(Beijing), 2015, 37(6): 510-516.

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戈谢氏病致病机制及治疗方法

Pathogenic mechanism and therapies for Gaucher’s disease

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