1. O-GlcNAcylation in health and neurodegenerative diseases
- Author
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Pann-Ghill Suh, Jae-Ick Kim, and Byeong Eun Lee
- Subjects
Aging ,Glycosylation ,Parkinson's disease ,Clinical Biochemistry ,Glycobiology ,Review Article ,Biology ,Biochemistry ,Neuroprotection ,Acetylglucosamine ,Diagnosis, Differential ,Serine ,O glcnacylation ,Functional importance ,Transcription (biology) ,Animals ,Homeostasis ,Humans ,Neurodegeneration ,Threonine ,Molecular Biology ,Neurons ,Brain ,Neurodegenerative Diseases ,Translation (biology) ,Alzheimer's disease ,Proteostasis ,Gene Expression Regulation ,Molecular Medicine ,Disease Susceptibility ,Protein Processing, Post-Translational ,Neuroscience ,Biomarkers - Abstract
O-GlcNAcylation is a posttranslational modification that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of many proteins. This protein modification interacts with key cellular pathways involved in transcription, translation, and proteostasis. Although ubiquitous throughout the body, O-GlcNAc is particularly abundant in the brain, and various proteins commonly found at synapses are O-GlcNAcylated. Recent studies have demonstrated that the modulation of O-GlcNAc in the brain alters synaptic and neuronal functions. Furthermore, altered brain O-GlcNAcylation is associated with either the etiology or pathology of numerous neurodegenerative diseases, while the manipulation of O-GlcNAc exerts neuroprotective effects against these diseases. Although the detailed molecular mechanisms underlying the functional roles of O-GlcNAcylation in the brain remain unclear, O-GlcNAcylation is critical for regulating diverse neural functions, and its levels change during normal and pathological aging. In this review, we will highlight the functional importance of O-GlcNAcylation in the brain and neurodegenerative diseases., Neurodegeneration: Sugar tags on proteins linked to brain disease The addition of a sugar tag called O-GlcNAc to proteins found in brain cells plays a critical role in regulating synaptic and neuronal function, with implications for understanding and treating neurodegenerative disease. Jae-Ick Kim and colleagues, Ulsan National Institute of Science and Technology, South Korea, review the ways in which the attachment or removal of O-GlcNAc sugars to or from proteins in the central nervous system can impact neuronal survival and the functional properties of neural circuits. In the aging brain, O-GlcNAc levels often become dysregulated, leading to aberrant protein activity that can fuel cognitive decline. In various neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, and amyotrophic lateral sclerosis, relevant disease-associated proteins often have abnormal O-GlcNAc patterns. Therapeutically altering the sugar-tagging process could potentially offer a new way of treating these brain disorders.
- Published
- 2021
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