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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Reduction of fetuin-A levels contributes to impairment of Purkinje cells in cerebella of patients with Parkinson's disease

  • Sunmi Yoon (BK21 Four Project, Department of Medical Sciences, Soonchunhyang University) ;
  • Napissara Boonpraman (BK21 Four Project, Department of Medical Sciences, Soonchunhyang University) ;
  • Chae Young Kim (BK21 Four Project, Department of Medical Sciences, Soonchunhyang University) ;
  • Jong-Seok Moon (Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University) ;
  • Sun Shin Yi (BK21 Four Project, Department of Medical Sciences, Soonchunhyang University)
  • Received : 2022.12.26
  • Accepted : 2023.03.14
  • Published : 2023.05.31
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Abstract

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 cerebellum function. However, few studies have reported 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 that regulate neuroinflammation in the cerebellum can be a beneficial therapeutic approach. Therefore, we employed PD patients and MPTP-induced PD mouse model to find cytokines involved in cerebellar neuroinflammation in PD and to examine changes in cell function by regulating related genes. Along with the establishment of a PD mouse model, abnormal shapes such as arrangement and number of Purkinje cells in the cerebellum were confirmed based on histological finding, consistent with those of cerebellums of PD patients. As a result of proteome profiling for neuroinflammation using PD mouse cerebellar tissues, fetuin-A, a type of cytokine, was found to be significantly reduced in Purkinje cells. To further elucidate the function of fetuin-A, neurons isolated from cerebellums of embryos (E18) were treated with fetuin-A siRNA. We uncovered that not only the population of neuronal cells, but also their morphological appearances were significantly different. 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 cerebellar Purkinje cells of mouse and human PD. In conclusion, morphological abnormalities of Purkinje cells in PD mice and patients have a close relationship with a decrease of fetuin-A, suggesting that diagnosis and treatment of cerebellar functions of PD patients might be possible through regulation of fetuin-A.

Keywords

Acknowledgement

This research was supported by a National Research Foundation (NRF) grant (NRF-2018R1D1A3B07047960) and Soonchunhyang University Research Fund.

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