摘要Neurodegenerative disorders are typically caused by harmful protein accumulation and nerve cell damage.A post-translational modification called O-linked N-acetylglucosamine ylation acts as a critical regulator in these disorders by controlling protein behavior,cell signaling,and energy balance.This modification is dynamically balanced through the cooperative actions of O-linked N-acetylglucosamine transferase and O-GlcNAcase.In healthy brains,O-GlcNAcylation supports nerve cell function and survival,but its imbalance contributes to disease progression.Notably,the effects of O-GlcNAcylation differ across disorders.This review reveals how O-GlcNAcylation bridges molecular mechanisms to neurodegeneration,as well as the prospects of targeted O-linked N-acetylglucosamine acylation therapy for neurodegenerative diseases.In Alzheimer's disease,it blocks toxic changes in key proteins like tau and amyloid-beta.In Parkinson's disease,it reduces the clumping of alpha-synuclein,yet may disrupt dopamine production.In amyotrophic lateral sclerosis,it protects nerve fiber transport systems.Additionally,O-GlcNAcylation plays an indispensable part in other neurodegenerative conditions,including Huntington's disease,aging,Machado-Joseph disease,multiple sclerosis,and giant axonal neuropathy.New therapies targeting this mechanism include glucosamine supplements and O-GlcNAcase inhibitors,which show clinical promise but face translational challenges.