Lessons from Drosophila models of DJ-1 deficiency.
Lessons from Drosophila models of DJ-1 deficiency.
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DOI：
10.1126/sageke.2006.2.pe2
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发表时间：
2006-01-11
期刊：
影响因子：
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通讯作者：
Dawson, Ted M
中科院分区：
文献类型：
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作者：
Moore, Darren J;Dawson, Valina L;Dawson, Ted M
DJ-1基因突变与罕见的常染色体隐性遗传早发性帕金森病（PD）有关。虽然DJ-1的确切生理功能仍然不清楚，但越来越多的证据表明，DJ-1可能在正常情况下作为氧化还原敏感的分子伴侣发挥作用，可以防止氧化应激的有害影响，特别是在线粒体中。最近对果蝇（Drosophila melanogaster）的研究进一步阐明了DJ-1的生物学作用。DJ-1缺陷果蝇模型表现出不同的表型，但共同突出了DJ-1对氧化损伤的突出神经保护作用。然而，缺乏DJ-1的果蝇并不总是产生有用的PD样表型（也就是说，它们通常不能表现出含有神经递质多巴胺的神经元的变性），这可能反映了假定的补偿性神经保护机制。DJ-1缺陷果蝇模型进一步突出了果蝇作为阐明蛋白质功能和模拟神经退行性疾病的重要工具的实用性。
Mutations in the DJ-1 gene are associated with rare forms of autosomal recessive early-onset Parkinson's disease (PD). Although the precise physiological function of DJ-1 remains obscure, accumulating evidence suggests that DJ-1 may normally function as a redox-sensitive molecular chaperone that can protect against the deleterious effects of oxidative stress, particularly in mitochondria. Recent studies in the fruit fly, Drosophila melanogaster, have shed further light on the biological role of DJ-1. DJ-1-deficient Drosophila models exhibit distinct phenotypes but collectively highlight a prominent neuroprotective role for DJ-1 against oxidative insult. However, Drosophila lacking DJ-1 do not consistently produce a useful PD-like phenotype (that is, they generally fail to exhibit degeneration of neurons that contain the neurotransmitter dopamine), which may reflect putative compensatory neuroprotective mechanisms. DJ-1-deficient fly models further highlight the utility of Drosophila as an important tool for elucidating protein function and for modeling neurodegenerative disease.