Comprehensive Perspectives on Experimental Models for Parkinson's Disease

Abstract

Parkinson's disease (PD) ranks second among the most common neurodegenerative diseases, characterized by progressive and selective loss of dopaminergic neurons. Various cross-species preclinical models, including cellular models and animal models, have been established through the decades to study the etiology and mechanism of the disease from cell lines to nonhuman primates. These models are aimed at developing effective therapeutic strategies for the disease. None of the current models can replicate all major pathological and clinical phenotypes of PD. Selection of the model for PD largely relies on our interest of study. In this review, we systemically summarized experimental PD models, including cellular and animal models used in preclinical studies, to understand the pathogenesis of PD. This review is intended to provide current knowledge about the application of these different PD models, with focus on their strengths and limitations with respect to their contributions to the assessment of the molecular pathobiology of PD and identification of the therapeutic strategies for the disease.

Keywords: Parkinson’s disease; cellular model; cross-species model; experimental model; transgenic animal.

Figure 1.

A cross-species platform for study of PD and drug test. From laboratory to clinical (bench to bedside), non-mammalian models such as cell lines, C. elegans, Drosophila and zebra fish offer an ideal and cost-effective drug screening and preliminary evaluation platform to explore hypothesized pathways or therapeutic targets. Rodent animal models, either toxin-induced or genetically established, could reproduce the lesion of DA or non-DA neurons and exhibit some of typical parkinsonian syndromes. Human iPSCs either derived from PD patients through reprogramming technology or established by gene-editing technology could provide a promising model for fundamental research and drug screening for PD. The comprised cross-species platform may accelerate the translation of laboratory research to clinical application.