In vivo modeling of prodromal stage of Parkinson's disease

Parkinson's disease (PD) has a long prodromal period that precedes the appearance of typical motor symptoms. This phase is extremely heterogeneous and is characterized by a wide range of non-motor alterations including REM sleep behavior disorders, constipation, olfactory and urinary dysfunctions. The increasing clinical and experimental knowledge on prodromal PD has led to the development of novel animal models recapitulating this disease stage as well as to a new use and interpretation of existing models. Prodromal animal models of PD represent an important tool for testing new therapeutic strategies and shedding light on the early pathogenic steps that set the ground for the extensive dopaminergic cell death observed in the midbrain. This review summarizes the new insights that these models have provided into the comprehension of a complex and still unexplored stage of PD.