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果蝇模型在研究铁代谢相关神经退行性疾病发病机制中的应用

朱周靓, 胡嘉隽, 钱忠明, 容永豪, 柯亚

香港中文大学医学院生物医学学院，香港；复旦大学药学院，上海 201203

摘要

铁代谢紊乱一直被视为是许多神经退行性疾病共同的病理特征，如阿尔茨海默氏症(Alzheimer’s disease, AD)、帕金森氏病(Parkinson’s disease, PD)以及弗里德赖希共济失调(Friedreich’s ataxia, FRDA)等均与脑铁代谢紊乱密切相关。随着分子生物学的进展，迄今为止也已经发现许多参与铁运输、储存和调控的基因与神经退行性病变的发生和发展有关，然而铁代谢紊乱在疾病发病过程中的致病机制仍不十分清楚。近年来许多研究者利用各种转基因动物模型来研究铁代谢相关神经退行性疾病的发病机制，但是啮齿类动物模型由于模型构建系统周期较长且比较复杂，从而限制了铁相关蛋白在神经退行性疾病中作用机制的研究进展。果蝇具有生活周期短暂、染色体数目少以及表型易于观察等优点，同时果蝇与人在很多基因和通路上都高度保守，且神经系统也可表现出与人相似的复杂的功能，因此被广泛地应用在铁代谢相关神经退行性疾病发病机制的研究中。果蝇还以其独特的分子遗传学优势，更容易构建缺失、插入、敲除或转基因模型，可在不同神经退行性病理情况下进行遗传学筛选铁相关的调控基因，从而为解决铁代谢紊乱在疾病发病过程中的致病机制提供更多的线索。因此在果蝇模型中发现可以中止甚至是逆转神经元退化进程的铁相关基因，以期为神经退行性疾病的研究和治疗提供策略。

关键词： 果蝇; 铁; 神经退行性疾病

分类号：Q426;Q581;R338

Drosophila models for studying iron-related neurodegenerative diseases

Zhou-Jing Zhu, Ka-Chun Wu, Zhong-Ming Qian, Wing-Ho Yung, Ya Ke

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China； Laboratory of Neuropharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China

Abstract

In recent years, iron has been regarded as a common pathological feature of many neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Friedreich’s ataxia (FRDA). A number of genes involved in iron transport, storage and regulation have been found associated with initiation and progression of neurodegeneration. However, whether iron abnormalities represent a primary or secondary event still remains unknown. Due to the limitation in transgenic rodent model construction and transfection systems, the progress in unraveling the pathogenic role of different iron-related proteins in neurodegenerative diseases has been slow. Drosophila melanogaster, a simple organism which has a shorter lifespan and smaller genome with many conserved genes, and captures many features of human nervous system and neurodegeneration, may help speed up the progress. The characteristics that spatial- and temporal-specific transgenic Drosophila can be easily constructed and raised in large quantity with phenotype easily determined turn Drosophila into an excellent in vivo genetic system for screening iron-related modifiers in different neurodegenerative conditions and hence provide a better picture about the pathogenic contribution of different iron-related protein abnormalities. It is believed that identification of important iron-related genes that can largely stop or even reverse degenerative process in Drosophila models may lead to development of novel therapeutic strategies against neurodegenerative diseases.

Key words: Drosophila; iron; neurodegenerative diseases

收稿日期：　　录用日期：

通讯作者：柯亚　　E-mail: yake@cuhk.edu.hk

引用本文：

朱周靓, 胡嘉隽, 钱忠明, 容永豪, 柯亚. 果蝇模型在研究铁代谢相关神经退行性疾病发病机制中的应用[J]. 生理学报 2014; 66 (1): 47-54.

Zhou-Jing Zhu, Ka-Chun Wu, Zhong-Ming Qian, Wing-Ho Yung, Ya Ke. Drosophila models for studying iron-related neurodegenerative diseases. Acta Physiol Sin 2014; 66 (1): 47-54 (in Chinese with English abstract).