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As a non-classical post-translational modification, O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) is widely found in human organ systems, particularly in our brains, and is indispensable for healthy cell biology. With the increasing age of the global population, the incidence of neurodegenerative diseases is increasing, too. The common characteristic of these disorders is the aggregation of abnormal proteins in the brain. Current research has found that O-GlcNAcylation dysregulation is involved in misfolding or aggregation of these abnormal proteins to mediate disease progression, but the specific mechanism has not been defined. This paper reviews recent studies on O-GlcNAcylation's roles in several neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, Machado-Joseph's disease, and giant axonal neuropathy, and shows that O-GlcNAcylation, as glucose metabolism sensor, mediating synaptic function, participating in oxidative stress response and signaling pathway conduction, directly or indirectly regulates characteristic pathological protein toxicity and affects disease progression. The existing results suggest that targeting O-GlcNAcylation will provide new ideas for clinical diagnosis, prevention, and treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • miR-204-3p is downregulated in Aβ-injected mice. • miR-204-3p upregulation alleviates neuroinflammation in Aβ-injected mice. • Dex upregulates miR-204-3p to alleviate neuroinflammation in Aβ-injected mice. • miR-204-3p targets and inhibits FBXL7 expression. • Dex eases neuroinflammation in AD model by the miR-204-3p/FBXL7 axis. Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by neuroinflammation. Dexmedetomidine (Dex) is known for its neuroprotective properties in clinical settings. In this study, we investigated the potential of Dex in protecting against neuroinflammation in an AD mouse model induced by amyloid-beta (Aβ) injection. First, in the AD mouse model, Aβ injection were administered, and the model was confirmed through behavioral tests, including the Morris water maze and Y-maze. Neuroinflammatory states in Aβ-injected mice were assessed using hematoxylin and eosin staining and enzyme-linked immunosorbent assay. Expression levels of microRNA (miR)-204-3p and F-box/LRR-repeat protein 7 (FBXL7) in mouse tissues were determined through real-time quantitative polymerase chain reaction and Western blot. The binding interaction between miR-204-3p and FBXL7 was elucidated using dual-luciferase analysis. Aβ-injected mice exhibited cognitive impairment, neuroinflammation, and downregulated miR-204-3p. Upregulation of miR-204-3p reduced inflammatory infiltration and mitigated neuroinflammation in Aβ-injected mice. Dex treatment reduced inflammation in hippocampal tissues of Aβ-injected mice. Dex treatment upregulated miR-204-3p, leading to suppressed FBXL7 expression in tissues. Inhibition of miR-204-3p or overexpression of FBXL7 reversed the alleviating effect of Dex on neuroinflammation in Aβ-injected mice. Overall, Dex increased miR-204-3p expression, resulting in the inhibition of FBXL7, and subsequently alleviated neuroinflammation in Aβ-injected mice. [ABSTRACT FROM AUTHOR]