Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease

Background: Parkinson's disease (PD) has become the fastest-growing neurodegenerative disorder worldwide. A valuable approach for unraveling the disease's mechanisms and new therapeutic targets involves investigating the PD-causing genes identified in families exhibiting the Mendelian inheritance of parkinsonism. Methods: In this article, we review how genetically modified mouse models can be employed to decipher the genetic architecture of PD. Results: We first discuss how well the human motor and non-motor symptoms of PD are currently evaluated in these PD mouse models, highlighting limitations. The pathogenic roles of five inherited PARK genes in PD are then extensively examined through their respective genetic mouse models in terms of phenotypic and cellular impacts. Furthermore, we discuss the strengths and weaknesses of existing transgenic mouse models and highlight significant accomplishments and advancements in this field from 2018 to the present. Conclusions: Building upon the current understanding of PD, we propose potential directions for enhancing genetic mouse models to further unveil the underlying mechanisms of PD and advance therapeutic research.