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O-GlcNAcylation regulates dopamine neuron function, survival and degeneration in Parkinson disease.

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.

SUBMITTER: Lee BE

PROVIDER: S-EPMC7805798 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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O-GlcNAcylation regulates dopamine neuron function, survival and degeneration in Parkinson disease.

Lee Byeong Eun BE Kim Hye Yun HY Kim Hyun-Jin HJ Jeong Hyeongsun H Kim Byung-Gyu BG Lee Ha-Eun HE Lee Jieun J Kim Han Byeol HB Lee Seung Eun SE Yang Yong Ryoul YR Yi Eugene C EC Hanover John A JA Myung Kyungjae K Suh Pann-Ghill PG Kwon Taejoon T Kim Jae-Ick JI

Brain : a journal of neurology 20201201 12

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-translat ...[more]

PMID: 33300544

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O-GlcNAcylation regulates dopamine neuron function, survival and degeneration in Parkinson disease.

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O-GlcNAcylation regulates dopamine neuron function, survival and degeneration in Parkinson disease.

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