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Brain Transcriptome Changes Associated With an Acute Increase of Protein O-GlcNAcylation and Implications for Neurodegenerative Disease.
J Neurochem
January 2025
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Enhancing protein O-GlcNAcylation by pharmacological inhibition of the enzyme O-GlcNAcase (OGA) has been considered as a strategy to decrease tau and amyloid-beta phosphorylation, aggregation, and pathology in Alzheimer's disease (AD). There is still more to be learned about the impact of enhancing global protein O-GlcNAcylation, which is important for understanding the potential of using OGA inhibition to treat neurodegenerative diseases. In this study, we investigated the acute effect of pharmacologically increasing O-GlcNAc levels, using the OGA inhibitor Thiamet G (TG), in normal mouse brains.
View Article and Find Full Text PDFIntracerebroventricular administration of a modified hexosaminidase ameliorates late-stage neurodegeneration in a GM2 mouse model.
PLoS One
January 2025
BioMarin Pharmaceutical Inc., Novato, CA, United States of America.
The GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease, are devastating neurodegenerative disorders caused by β-hexosaminidase A (HexA) deficiency. In the Sandhoff disease mouse model, rescue potential was severely reduced when HexA was introduced after disease onset. Here, we assess the effect of recombinant HexA and HexD3, a newly engineered mimetic of HexA optimized for the treatment of Tay-Sachs disease and Sandhoff disease.
View Article and Find Full Text PDFOlive leaf extract (OLE) reduces mast cell-mediated allergic inflammation.
Biomed Pharmacother
January 2025
Department of Pharmacy, School of Medicine, University of Naples Federico II, Naples, Italy. Electronic address:
Mast cell-mediated reactions promote various allergic disease, including anaphylaxis, allergic rhinitis, asthma, and atopic dermatitis. Different data demonstrated an intricate relationship between the use of antihistaminic drugs, the onset of side effects, and the development of resistance, underscoring the importance to find novel therapeutic approaches to treat allergic diseases. Olive leaf extract (OLE), is a by-product of the olive tree rich in bioactive compounds, known for its numerous therapeutic properties, including antioxidant, anti-tumoral and antidiabetic effects.
View Article and Find Full Text PDFClinical and biochemical abnormalities in a feline model of GM2 activator deficiency.
Mol Genet Metab
January 2025
Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, AL 36849, United States of America; Department of Anatomy, Physiology & Pharmacology, College of Veterinary Medicine, Auburn University, AL 36849, United States of America. Electronic address:
Though it has no catalytic activity toward GM2 ganglioside, the GM2 activator protein (GM2A) is essential for ganglioside hydrolysis by facilitating the action of lysosomal ß-N-acetylhexosaminidase. GM2A deficiency results in death in early childhood due to rapid central nervous system deterioration similar to the related GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease. This manuscript further characterizes a feline model of GM2A deficiency with a focus on clinical and biochemical parameters that may be useful as benchmarks for translational therapeutic research.
View Article and Find Full Text PDFPERM1 regulates mitochondrial energetics through O-GlcNAcylation in the heart.
J Mol Cell Cardiol
January 2025
Fralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech, Roanoke, VA, USA; Center for Vascular and Heart Research, Fralin Biomedical Research Institute, Virginia Tech, Roanoke, VA, USA; Department of Human Nutrition, Food and Exercise, Virginia Tech, Blacksburg, VA, USA. Electronic address:
PERM1 was initially identified as a new downstream target of PGC-1α and ERRs that regulates mitochondrial bioenergetics in skeletal muscle. Subsequently, we and other groups demonstrated that PERM1 is also a positive regulator of mitochondrial bioenergetics in the heart. However, the exact mechanisms of regulatory functions of PERM1 remain poorly understood.
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