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斑马鱼模型对帕金森病的前景:当今的科学与未来的治疗

The Promise of the Zebrafish Model for Parkinson's Disease: Today's Science and Tomorrow's Treatment.

作者信息

Razali Khairiah, Othman Noratikah, Mohd Nasir Mohd Hamzah, Doolaanea Abd Almonem, Kumar Jaya, Ibrahim Wisam Nabeel, Mohamed Ibrahim Norlinah, Mohamed Wael M Y

机构信息

Department of Basic Medical Sciences, Kulliyyah of Medicine, International Islamic University Malaysia (IIUM), Kuantan, Malaysia.

Department of Basic Medical Sciences, Kulliyyah of Nursing, International Islamic University Malaysia (IIUM), Kuantan, Malaysia.

出版信息

Front Genet. 2021 Apr 15;12:655550. doi: 10.3389/fgene.2021.655550. eCollection 2021.

Abstract

The second most prevalent neurodegenerative disorder in the elderly is Parkinson's disease (PD). Its etiology is unclear and there are no available disease-modifying medicines. Therefore, more evidence is required concerning its pathogenesis. The use of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the basis of most animal models of PD. MPTP is metabolized by monoamine oxidase B (MAO B) to MPP + and induces the loss of dopaminergic neurons in the substantia nigra in mammals. Zebrafish have been commonly used in developmental biology as a model organism, but owing to its perfect mix of properties, it is now emerging as a model for human diseases. Zebrafish () are cheap and easy to sustain, evolve rapidly, breed transparent embryos in large amounts, and are readily manipulated by different methods, particularly genetic ones. Furthermore, zebrafish are vertebrate species and mammalian findings obtained from zebrafish may be more applicable than those derived from genetic models of invertebrates such as and . The resemblance cannot be taken for granted, however. The goal of the present review article is to highlight the promise of zebrafish as a PD animal model. As its aminergic structures, MPTP mode of action, and PINK1 roles mimic those of mammalians, zebrafish seems to be a viable model for studying PD. The roles of zebrafish MAO, however, vary from those of the two types of MAO present in mammals. The benefits unique to zebrafish, such as the ability to perform large-scale genetic or drug screens, should be exploited in future experiments utilizing zebrafish PD models.

摘要

帕金森病(PD)是老年人中第二常见的神经退行性疾病。其病因尚不清楚,且尚无有效的疾病改善药物。因此,需要更多关于其发病机制的证据。神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)的使用是大多数帕金森病动物模型的基础。MPTP被单胺氧化酶B(MAO B)代谢为MPP +,并导致哺乳动物黑质中多巴胺能神经元的丧失。斑马鱼在发育生物学中一直被用作模式生物,但由于其完美的特性组合,它现在正成为一种人类疾病模型。斑马鱼价格便宜且易于饲养,进化迅速,能大量繁殖透明胚胎,并且易于通过不同方法进行操作,特别是基因操作方法。此外,斑马鱼是脊椎动物物种,从斑马鱼获得的哺乳动物研究结果可能比从诸如果蝇和线虫等无脊椎动物基因模型获得的结果更适用。然而,这种相似性不能被视为理所当然。本综述文章的目的是强调斑马鱼作为帕金森病动物模型的前景。由于其胺能结构、MPTP作用模式和PINK1作用与哺乳动物相似,斑马鱼似乎是研究帕金森病的可行模型。然而,斑马鱼MAO的作用与哺乳动物中存在的两种MAO的作用不同。斑马鱼独有的优势,如进行大规模基因或药物筛选的能力,应在未来利用斑马鱼帕金森病模型的实验中加以利用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f9/8082503/d904e59bbcab/fgene-12-655550-g001.jpg

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