Development of a model system for neuronal dysfunction in Fabry disease

被引：13

作者：

Kaneski, Christine R. ^{[1
]}

Brady, Roscoe O. ^{[1
]}

Hanover, John A. ^{[2
]}

Schueler, Ulrike H. ^{[2
]}

机构：

[1] NINDS, NIH, Bethesda, MD 20892 USA

[2] NIDDK, NIH, Bethesda, MD 20892 USA

来源：

MOLECULAR GENETICS AND METABOLISM | 2016年 / 119卷 / 1-2期

基金：

美国国家卫生研究院;

关键词：

Acetylcholine; Alpha-galactosidase A; Fabty disease; Gene silencing; Neuropathy; HUMAN NEUROBLASTOMA-CELLS; VESICULAR ACETYLCHOLINE TRANSPORTER; ALPHA-GALACTOSIDASE; LA-N-2; DIFFERENTIATION; FIBROBLASTS; EXPRESSION; GROWTH; ASSAY; PAIN;

D O I：

10.1016/j.ymgme.2016.07.010

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Fabry disease is a glycosphingolipid storage disorder that is caused by a genetic deficiency of the enzyme alphagalactosidase A (AGA, EC 3.2.1.22). It is a multisystem disease that affects the vascular, cardiac, renal, and nervous systems. One of the hallmarks of this disorder is neuropathic pain and sympathetic and parasympathetic nervous dysfunction. The exact mechanism by which changes in AGA activity result in change in neuronal function is not clear, partly due to of a lack of relevant model systems. In this study, we report the development of an in vitro model system to study neuronal dysfunction in Fabry disease by using short-hairpin RNA to create a stable knock-down of AGA in the human cholinergic neuronal cell line, LA-N-2. We show that gene-silenced cells show specifically reduced AGA activity and store globotriaosylceramide. In gene-silenced cells, release of the neurotransmitter acetylcholine is significantly reduced, demonstrating that this model may be used to study specific neuronal functions such as neurotransmitter release in Fabry disease. Published by Elsevier Inc.

引用

页码：144 / 150

页数：7

共 43 条

[1] Elevated globotriaosylsphingosine is a hallmark of Fabry disease [J].