Phenotypic features such as ataxia and loss of motor function, which are characteristics of Parkinson's disease (PD), are expected to be very closely related to the operation of the cerebellum. Still, surprisingly, many researchers are not interested in identifying the function of the cerebellum. Since the cerebellum, like the cerebrum, is known to undergo functional and morphological changes due to neuroinflammatory processes, elucidating key functional factors which regulate neuroinflammation in the cerebellum can be a beneficial therapeutic approach. Therefore, we employed the PD patients and MPTP-induced PD mouse model to find cytokines that are involved in cerebellar neuroinflammation in PD and to examine the changes in cell function by regulating related genes. Along with the establishment of the PD mouse model, abnormal shapes such as arrangement, number, and morphology of Purkinje cells in the cerebellum were confirmed in the histological finding, which were consistent with those of the cerebellum of PD patients. As a result of proteome profiling that participates in neuroinflammation using PD mouse cerebellar tissue, fetuin-A, which is a type of cytokine, was significantly reduced in Purkinje cells. To further elucidate the function of fetuin-A, we uncovered that not only the population of neuronal cells but also their morphological appearances were significantly different when the neurons isolated from the cerebellum of embryos (E18) were treated with fetuin-A siRNA.
In this study, we found a functional gene called fetuin-A in the PD model's cerebellum, which was closely related to the role of Purkinje cells within the cerebellum of mouse and human PD. In conclusion, because the morphological abnormalities of Purkinje cells in PD mice and patients have a close relationship with the decreasing fetuin-A, we expect that the diagnosis and treatment of cerebellar function in PD patients will be possible through the regulation of fetuin-A.