Roles of O-GlcNAcylation on amyloid-beta precursor protein processing, tau phosphorylation, and hippocampal synapses dysfunction in Alzheimer's disease

摘要

Alzheimer disease (AD), a central nervous system degenerative disease, is characterized by abnormal deposition of amyloid-beta peptide (A beta), neurofibrillary tangles formed by hyperphosphorylated tau and synaptic loss. It is widely accepted that A beta is the chief culprit of AD. A beta peptide is the cleavage product of amyloid-beta precursor protein (APP). Recently, more attention has been paid to O-linked beta-N-acetylglucosaminylation (O-GlcNAcylation) modification of protein. O-GlcNAcylation plays a significant role in hippocampal synaptic function. Abated O-GlcNAcylation might be a modulator in progression of AD through regulating activity of pertinent enzymes and factors. Evidence suggests that enhanced O-GlcNAcylation interacts with tau phosphorylation and prevents brain from tau and A beta-induced impairment. Here, we review the roles of O-GlcNAcylation in APP cleavage, tau phosphorylation and hippocampal synapses function.