A Critical Review of Zebrafish Models of Parkinson's Disease.

Jillian M Doyle,Roger P Croll

doi:10.3389/fphar.2022.835827

Abstract

A wide variety of human diseases have been modelled in zebrafish, including various types of cancer, cardiovascular diseases and neurodegenerative diseases like Alzheimer’s and Parkinson’s. Recent reviews have summarized the currently available zebrafish models of Parkinson’s Disease, which include gene-based, chemically induced and chemogenetic ablation models. The present review updates the literature, critically evaluates each of the available models of Parkinson’s Disease in zebrafish and compares them with similar models in invertebrates and mammals to determine their advantages and disadvantages. We examine gene-based models, including ones linked to Early-Onset Parkinson’s Disease: PARKIN, PINK1, DJ-1, and SNCA; but we also examine LRRK2, which is linked to Late-Onset Parkinson’s Disease. We evaluate chemically induced models like MPTP, 6-OHDA, rotenone and paraquat, as well as chemogenetic ablation models like metronidazole-nitroreductase. The article also reviews the unique advantages of zebrafish, including the abundance of behavioural assays available to researchers and the efficiency of high-throughput screens. This offers a rare opportunity for assessing the potential therapeutic efficacy of pharmacological interventions. Zebrafish also are very amenable to genetic manipulation using a wide variety of techniques, which can be combined with an array of advanced microscopic imaging methods to enable in vivo visualization of cells and tissue. Taken together, these factors place zebrafish on the forefront of research as a versatile model for investigating disease states. The end goal of this review is to determine the benefits of using zebrafish in comparison to utilising other animals and to consider the limitations of zebrafish for investigating human disease.

Highlights

1.1 Parkinson’s DiseaseParkinson’s Disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s Disease
This study examined the expression of Parkinson’s DiseaseParkinson’s Disease (PD)-related genes and found that in treated fish, dj-1 was down-regulated by 60% and lrrk2 was up-regulated
The CRISPR/Cas9 system shows immense promise for the creation of genetically altered zebrafish lines and this genomic editing technique presents an opportunity to create more accurate gene knock downs/ins, which may elucidate some of the gene functions that are unclear in other models

Summary

Introduction

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s Disease. It typically affects individuals over the age of 65, Early Onset Parkinson’s Disease (EOPD) is well-noted. Symptoms primarily affect movement, including tremors, bradykinesia (slow movements), rigidity and postural instability; in addition, patients may manifest cognitive symptoms like impaired memory and executive dysfunction (Rana et al, 2015). Numerous genes have been implicated, including, but not limited to: LRRK2, SNCA (PARK1/4), DJ-1, PINK1, and PARKIN (Best and Alderton, 2008). Environmental factors, like chemical exposure to MPTP, pesticides and solvents, may play a role in the onset of PD (Best and Alderton, 2008; Vázquez-Vélez and Zoghbi, 2021)

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Conclusion