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Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and subsequent motor symptoms, but various non-motor symptoms (NMS) often precede motor symptoms. Recently, NMS have attracted much attention as a clue for identifying patients in a prodromal stage of PD, which is an excellent point at which to administer disease-modifying therapies (DMTs). These prodromal symptoms include olfactory loss, constipation, and sleep disorders, especially rapid eye movement sleep behavior disorder (RBD), all of which are also important for elucidating the mechanisms of the initiation and progression of the disease. For the development of DMTs, an animal model that reproduces the prodromal stage of PD is also needed. There have been various mammalian models reported, including toxin-based, genetic, and alpha synuclein propagation models. In this article, we review the animal models that exhibit NMS as prodromal symptoms and also discuss an appropriate prodromal model and its importance for the development of DMT of PD.
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