Do animal models represent the diversity of clinical Parkinson's disease?

Parkinson's disease (PD) is a multifactorial and progressive neurodegenerative disorder characterized by a complex symptomatology, including a broad spectrum of motor and non-motor symptoms. Disease modeling in animals represents a keystone part of the research aimed at understanding molecular bases driving PD onset, and specific mechanisms shaping pathological trajectories along disease progression, sustaining the inter-individual variability in PD manifestation. Multiple experimental approaches using toxins, viral vectors, and genetic perturbations have been developed to reproduce key PD features in animals, resulting in a wide variety of models. However, a minority of models show multiple aspects of PD-related phenomenology. In this short review, we provide a synthetic description of selected rodent PD models, including those based on stronger etiological construct validity as well as newly developed models, and discuss their strengths and limitations in reproducing PD features. The main intention is to provide a simple resource for selecting optimal PD models that show multiple histopathological and behavioral alterations, thus more closely mirroring clinical PD complexity.