Rodent models and accompanying in vitro strategies for studying the etiology and therapy of Parkinson's disease

The lack of disease-modifying therapies for Parkinson's disease (PD) places a severe burden on patients, their caregivers and aging societies. While the incomplete knowledge of underlying causes and pathophysiology remains a major bottleneck towards the development of rational therapies, there have been important advances in our understanding of neurodegenerative processes. Here, animal models have contributed substantially by allowing researchers to decipher PD-relevant pathology and the development of corresponding behavioral signs, which enabled development and refinement of treatment options. Without animal models, hypotheses of mechanisms underlying the development of motor symptoms after dopamine depletion, dyskinesia as side effects, the impact of diverse environmental neurotoxins, or the formation of alpha-synuclein pathology and spreading could not have been conclusively tested. Likewise, novel technologies are enabling the use of patient derived tissues for generating in vitro models that further enhance our understanding of mechanisms and of the effects of specific genetic modifications and their role in neurodegeneration. However, animal models are, as of yet, still required to model a fully functional central nervous system connected to the immune system and peripheral organs, which are impacted by the diversity of PD pathology and symptoms. Here, we provide an overview of key contributions of animal models, their ongoing role in PD research, and how this research can be enhanced by the concomitant use of advanced in vitro systems.