한빛사 논문
Byeong Eun Lee,1 Hye Yun Kim,1 Hyun-Jin Kim,1 Hyeongsun Jeong,1 Byung-Gyu Kim,2 Ha-Eun Lee,1 Jieun Lee,1 Han Byeol Kim,3 Seung Eun Lee,4 Yong Ryoul Yang,5 Eugene C. Yi,3 John A. Hanover,6 Kyungjae Myung,1,2 Pann-Ghill Suh,1,7 Taejoon Kwon1 and Jae-Ick Kim1,*
1 School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
2 Center for Genomic Integrity, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea
3 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Medicine and College of Pharmacy, Seoul National University, Seoul 03080, Republic of Korea
4 Research Animal Resource Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
5 Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea
6 Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney (NIDDK), National Institute of Health (NIH), Bethesda, Maryland, USA
7 Korea Brain Research Institute (KBRI), Daegu 41062, Republic of Korea
*Correspondence to: Jae-Ick Kim, PhD
School of Life Sciences, Building 110, Room 601-5, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
Abstract
The dopamine system in the midbrain is essential for volitional movement, action selection, and reward-related learning. Despite its versatile roles, it contains only a small set of neurons in the brainstem. These dopamine neurons are especially susceptible to Parkinson’s disease and prematurely degenerate in the course of disease progression, while the discovery of new therapeutic interventions has been disappointingly unsuccessful. Here, we show that O-GlcNAcylation, an essential post-translational modification in various types of cells, is critical for the physiological function and survival of dopamine neurons. Bidirectional modulation of O-GlcNAcylation importantly regulates dopamine neurons at the molecular, synaptic, cellular, and behavioural levels. Remarkably, genetic and pharmacological upregulation of O-GlcNAcylation mitigates neurodegeneration, synaptic impairments, and motor deficits in an animal model of Parkinson’s disease. These findings provide insights into the functional importance of O-GlcNAcylation in the dopamine system, which may be utilized to protect dopamine neurons against Parkinson’s disease pathology.
Keywords: dopamine neuron, O-GlcNAcylation, Parkinson’s disease, α-synuclein, neuronal survival
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