Loss of spastic paraplegia gene atlastin induces age-dependent death of dopaminergic neurons in Drosophila

被引：31
作者：
Lee, Youngseok
Paik, Donggi
Bang, Sunhoe
Kang, Jongkyun
Chun, Bumkoo
Lee, Seungbok
Bae, Eunkyung
Chung, Jongkyung
Kim, Jaeseob
机构：
[1] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea
[2] Seoul Natl Univ, Sch Dent, Dept Cell & Dev Biol, Seoul 110740, South Korea
[3] Korea Adv Inst Sci & Technol, GenExel Sein Inst, Taejon 305701, South Korea
来源：
NEUROBIOLOGY OF AGING | 2008年 / 29卷 / 01期
关键词：
hereditary spastic paraplegia; atlastin; neuronal degeneration; dopaminergic neurons; bang-sensitive; targeted expression;
D O I：
10.1016/j.neurobiolaging.2006.09.004
中图分类号：
R592 [老年病学]; C [社会科学总论];
学科分类号：
03 ; 0303 ; 100203 ;
摘要：
Hereditary spastic paraplegias (HSPs) are human genetic disorders causing increased stiffness and overactive muscle reflexes in the lower extremities. atlastin (ad) is one of the major genes in which mutations result in HSP. We generated a Drosophila model of HSP that has a null mutation in atl. As they aged, atl null flies were paralyzed by mechanical shock such as bumping or vortexing. Furthermore, the flies showed age-dependent degeneration of dopaminergic neurons. These phenotypes were rescued by targeted expression of atl in dopaminergic neurons or feeding L-DOPA or SK&F 38393, an agonist of dopamine receptor. Our data raised the possibility that one of the causes of HSP disease symptoms in human patients with all mutations is malfunction or degeneration of dopaminergic neurons. (C) 2006 Elsevier Inc. All rights reserved.
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收藏
页码：84 / 94
页数：11
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