Lee, Byeong Eun Kim, Hye Yun Kim, Hyun-Jin Jeong, Hyeongsun Kim, Byung-Gyu Lee, Ha-Eun Lee, Jieun Kim, Han Byeol Lee, Seung Eun Yang, Yong Ryoul Yi, Eugene C. Hanover, John A. Myung, Kyungjae Suh, Pann-Ghill Kwon, Taejoon Kim, Jae-Ick 2024-01-19T16:02:47Z 2024-01-19T16:02:47Z 2021-09-02 2020-12 0006-8950 https://pubs.kist.re.kr/handle/201004/117792 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. English OXFORD UNIV PRESS O-GlcNAcylation regulates dopamine neuron function, survival and degeneration in Parkinson disease Article 10.1093/brain/awaa320 1 BRAIN, v.143, pp.3699 - 3716 BRAIN 143 3699 3716 scie scopus 000615920000029 2-s2.0-85100070424 Clinical Neurology Neurosciences Neurosciences & Neurology Article dopamine neuron O-GlcNAcylation Parkinson&apos s disease alpha-synuclein neuronal survival