The emerging link between O-GlcNAc and Alzheimer disease

Regional glucose hypometabolism is a defining feature of Alzheimer disease (AD). One emerging link between glucose hypometabolism and progression of AD is the nutrient-responsive post-translational O-GlcNAcylation of nucleocytoplasmic proteins. O-GlcNAc is abundant in neurons and occurs on both tau and amyloid precursor protein. Increased brain O-GlcNAcylation protects against tau and amyloid-β peptide toxicity. Decreased O-GlcNAcylation [...]

October 21st, 2014|Tags: , , , , , , , , , , |

Chronic O-β-N-acetylglucosaminylase inhibition with Thiamet-G prevents tau pathology and hyperactivity in rTg4510 mice

Background: The abnormal hyperphosphorylation of the microtubule-associated protein tau plays a crucial role in neurodegeneration in Alzheimer's disease (AD) and aggregation of hyperphosphorylated tau into neurofibrillary tangles is a hallmark brain lesion in AD. Besides kinases and phosphatases tau phosphorylation is regulated by O-GlcNAcylation, a posttranslational modification of proteins on the serine or threonine residues with [...]

September 6th, 2014|Tags: , , , , , |

Increased O-GlcNAcylation reduces pathological tau without affecting its normal phosphorylation in a mouse model of tauopathy

Neurofibrillary tangles (NFT), mainly consisting of fibrillar aggregates of hyperphosphorylated tau, are a defining pathological feature of Alzheimer's Disease and other tauopathies. Progressive accumulation of tau into NFT is considered to be a toxic cellular event causing neurodegeneration. Tau is subject to O-linked N-acetylglucosamine (O-GlcNAc) modification and O-GlcNAcylation of tau has been suggested to regulate [...]

December 8th, 2013|Tags: , , , , , |