Oct 26, 2014 – Alectos today announced publication of preclinical studies showing that pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in the TAPP mouse model of Alzheimer’s disease. For details, see: Yuzwa, S.A. et al. Mol Neurodegener 9:42 (2014).
Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice
BACKGROUND: Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. It remains unknown, however, if O-GlcNAc can influence the formation of [...]
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 [...]
O-GlcNAc and neurodegeneration: biochemical mechanisms and potential roles in Alzheimer’s disease and beyond
Alzheimer disease (AD) is a growing problem for aging populations worldwide. Despite significant efforts, no therapeutics are available that stop or slow progression of AD, which has driven interest in the basic causes of AD and the search for new therapeutic strategies. Longitudinal studies have clarified that defects in glucose metabolism occur in patients exhibiting [...]
O-linked β-N-acetylglucosaminidase inhibitor attenuates β-amyloid plaque and rescues memory impairment
Deposition of β-amyloid (Aβ) as senile plaques and disrupted glucose metabolism are two main characteristics of Alzheimer's disease (AD). It is unknown, however, how these two processes are related in AD. Here we examined the relationship between O-GlcNAcylation, which is a glucose level-dependent post-translational modification that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to proteins, and Aβ production [...]