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1부 초청강연 SessionⅠ Glycobiology and human disease

The couple of netrin-1/α-Synuclein regulates the survial of dopaminergic neurons via α-Synuclein disaggregation

초록

영어

α-Synuclein has been proposed to play a key pathogen in Parkinson's disease (PD). Especially, the abnormal accumulation and aggregation of the misfolded α-Synuclein protein is the neuropathological hallmark of all α-Synucleinopathies, including Parkinson's disease. Netrins (netrin-1, netrin-3, and netrin-4) are secreted proteins, which are laminin-related and involved in axon guidance function and cell survival molecular pathway. Remarkably, only netrin-1 is highly expressed in healthy adult substantia nigra brain region and inversely correlates with the expression of α-Synuclein, which led us to investigate the impact of the molecular interaction between α-Synuclein and netrin-1 in dopaminergic neuron fate. Here we show that netrin-1 and α-Synuclein directly interact in pre-formed fibrils (PFFs) generation test and real time binding assay. Strikingly, we observed that the level of netrin-1 was significantly decreased in SNCA Tg mouse brain with dopaminergic cell death, which matched the analysis result from human PD patients database. Our finding suggest that netrin-1 deprivation triggers dopaminergic neuronal cell death with α-Synuclein aggregation during aging process and netrin-1 can be the promising therapeutic or diagnostic molecule in α-Synucleinopathies.

저자정보

  • Seung Min Jang Department of Physiology, College of Medicine, Hallym University
  • Eun Ji Kang Department of Physiology, College of Medicine, Hallym University
  • Ye Ji Lee Department of Physiology, College of Medicine, Hallym University
  • Ho Sun Jeon Department of Physiology, College of Medicine, Hallym University
  • Dae Ki Hong Department of Physiology, College of Medicine, Hallym University
  • Song Hee Lee Department of Physiology, College of Medicine, Hallym University
  • Xia Liu Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
  • Seong Su Kang Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
  • Eun Hee Ahn Department of Physiology, College of Medicine, Hallym University

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