Animal models of Parkinson's disease: An updated overview

Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology, besides a minority of genetic cases, is still largely unknown. Animal models have contributed to elucidate PD etiology and pathogenesis, as well as its cellular and molecular mechanisms, leading to the general hypothesis that this neurological disorder is due to complex interactions between environmental and genetic factors. However, the full understanding of PD is still very far from being achieved, and new potential treatments need to be tested to further improve patients' quality of life and, possibly, slow down the neurodegenerative process. In this context, animal models of PD are required to address all these issues. "Classic" models are based on neurotoxins that selectively target catecholaminergic neurons (such as 6-hydroxydopamine, 1-methyl-1,2,3,6-tetrahydropiridine, agricultural pesticides, etc.), while more recent models employ genetic manipulations that either introduce mutations similar to those find in familial cases of PD (α-synuclein, DJ-1, PINK1, Parkin, etc.) or selectively disrupt nigrostriatal neurons (MitoPark, Pitx3, Nurr1, etc.). Each one of these models has its own advantages and limitations, thus some are better suited for studying PD pathogenesis, while others are more pertinent to test therapeutic treatments. Here, we provide a critical and updated review of the most used PD models.