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对成年斑马鱼中MPTP诱导的帕金森氏症进行综述,以探索针对人类帕金森病的药物干预措施。

A review of MPTP-induced parkinsonism in adult zebrafish to explore pharmacological interventions for human Parkinson's disease.

作者信息

Bagwell Emmeline, Larsen Jessica

机构信息

Department of Bioengineering, Clemson University, Clemson, SC, United States.

Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, SC, United States.

出版信息

Front Neurosci. 2024 Aug 7;18:1451845. doi: 10.3389/fnins.2024.1451845. eCollection 2024.

Abstract

Novel work in adult zebrafish, to recapitulate human neurodegenerative disease has proven useful in both pharmaceutical development and research on genetic disease. Due to high genetic homology to humans, affordable husbandry, relatively quick life cycle breeding times, and robust embryo production, zebrafish offer a promising model to test pharmaceutical performance in a high throughput, setting. Currently, most research in zebrafish models of Parkinson's disease induces the disease in larval or embryonic stage organisms due to ease of administration, with advancement through developmental stages taking only a matter of days. The use of early-stage organisms limits the usability of zebrafish as models for adult disease and specifically age-related neurodegenerative conditions. Recently, researchers have sought to extend the usability of zebrafish into models for Parkinson's disease. Specifically, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has emerged as a prodrug that upon injection well-encompasses the biochemical mechanisms and symptomology associated with Parkinson's disease. By utilizing MPTP in an adult zebrafish model, advancements in Parkinson's disease research may be achieved. This paper highlights the recent research on this model, comparing it to the human form of Parkinson's disease.

摘要

在成年斑马鱼身上开展的、用于模拟人类神经退行性疾病的新研究,已证明在药物研发和遗传疾病研究中都很有用。由于与人类具有高度的基因同源性、养殖成本低、生命周期相对较短且繁殖速度快,以及能大量产出胚胎,斑马鱼为在高通量环境下测试药物性能提供了一个很有前景的模型。目前,在帕金森病斑马鱼模型中的大多数研究都是在幼虫或胚胎期生物体中诱发疾病,因为给药方便,而且从发育阶段进展到成年只需几天时间。使用早期生物体限制了斑马鱼作为成人疾病模型,特别是与年龄相关的神经退行性疾病模型的可用性。最近,研究人员试图将斑马鱼的可用性扩展到帕金森病模型中。具体来说,1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)已成为一种前体药物,注射后能很好地涵盖与帕金森病相关的生化机制和症状。通过在成年斑马鱼模型中使用MPTP,可能会在帕金森病研究方面取得进展。本文重点介绍了对该模型的最新研究,并将其与人类形式的帕金森病进行了比较。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75df/11335677/e918ddbdba8b/fnins-18-1451845-g001.jpg

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