There is increasing evidence pointing to the digestive system as a key etiopathogenetic factor in Parkinson's disease (PD). Gastrointestinal symptoms are prevalent and occur during the prodromal stage of the disease, and pathological aggregates of alpha-synuclein (ɑS) in the enteric nervous system (ENS) have been observed before their accumulation in the brain. Bacterial and dietary synucleins could be important triggers for ɑS aggregation in the ENS; however, the absorption and translocation of luminal ɑS have not yet been thoroughly investigated. The aim of this thesis was to establish and validate an ex vivo model of luminal ɑS translocation through the digestive mucosa of mice and rats, and to examine the mechanisms of this translocation. The studies conducted as part of this thesis demonstrated that ex vivo incubation of fluorescently labeled αS with the digestive mucosa can serve as a valuable model for studying pathophysiological mechanisms related to synucleinopathies. Following luminal exposure, exogenous αS was predominantly found in epithelial cells (including epithelial cells shed into the lumen). Subsequently, luminal αS accumulates in cells expressing markers of enteroendocrine and neuronal cells. The most significant original contribution of this thesis is the accumulation of αS in enteroglial cells, a finding that has not been previously described in the literature. The working model proposed based on this research suggests the translocation of luminal αS through digestive epithelial cells, followed by accumulation in the extensions of neuronal and enteroglial cells, which could be key mediators in the transfer to ENS networks. Understanding the translocation of αS in the digestive system could contribute to the development of novel targeted therapies that may prevent the onset and slow the progression of PD.