ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2021
The Dysregulation of OGT/OGA Cycle Mediates Tau and APP Neuropathology in Down Syndrome.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Role of O-GlcNAcylation in Central Nervous System Development and Injuries: A Systematic Review.Molecular neurobiology · 2024Pooled it
- Genetic Rescue of Pathogenic O-GlcNAc Dyshomeostasis Associated with Microcephaly and Motor Deficits.eNeuro · 2026Article
- Loss of Proteostasis and Early-Onset Neurodegeneration in Down Syndrome: From Mechanisms to Interventions.Antioxidants (Basel, Switzerland) · 2026Review
- Notch1 O-GlcNAcylation drives tumor stemness and mechanoadaptation to a stiff microenvironment and promotes chordoma recurrence.The Journal of clinical investigation · 2026Article
- Pharmacological inhibition of O-GlcNAcase reduces pS129-α-synuclein positive aggregates in the substantia nigra of mThy1-hSNCA mice.Journal of Parkinson's disease · 2026Article
- Targeting O-GlcNAcylation: Novel Therapeutic Strategies for Neurological Disease.Molecular neurobiology · 2025Review
- Brain O-GlcNAcylation: Bridging physiological functions, disease mechanisms, and therapeutic applications.Molecular psychiatry · 2025Review
- Examining the effects of extremely low-frequency magnetic fields on cognitive functions and functional brain markers in aged mice.Scientific reports · 2025Article
- Astragalus polysaccharide treatment relieves cerebral ischemia‒reperfusion injury by promoting M2 polarization of microglia by enhancing O-GlcNAcylation.Metabolic brain disease · 2024Article
- Aging exacerbates oxidative stress and liver fibrosis in an animal model of Down Syndrome.Aging · 2024Article
- Understanding and exploiting the roles of O-GlcNAc in neurodegenerative diseases.The Journal of biological chemistry · 2023Review
- Chemical Biology Approaches to Understanding Neuronal O-GlcNAcylation.Israel journal of chemistry · 2023Article
- O-GlcNAcylation is crucial for sympathetic neuron development, maintenance, functionality and contributes to peripheral neuropathy.Frontiers in neuroscience · 2023Article
- Consequences of chromosome gain: A new view on trisomy syndromes.American journal of human genetics · 2022Review
- The interplay among oxidative stress, brain insulin resistance and AMPK dysfunction contribute to neurodegeneration in type 2 diabetes and Alzheimer disease.Free radical biology & medicine · 2021Review
- High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer's Disease Signatures.International journal of molecular sciences · 2021Article
- Stress Responses in Down Syndrome Neurodegeneration: State of the Art and Therapeutic Molecules.Biomolecules · 2021Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Protein O-GlcNAcylation is a nutrient-related post-translational modification that, since its discovery some 30 years ago, has been associated with the development of neurodegenerative diseases. As reported in Alzheimer's disease (AD), flaws in the cerebral glucose uptake translate into reduced hexosamine biosynthetic pathway flux and subsequently lead to aberrant protein O-GlcNAcylation. Notably, the reduction of O-GlcNAcylated proteins involves also tau and APP, thus promoting their aberrant phosphorylation in AD brain and the onset of AD pathological markers. Down syndrome (DS) individuals are characterized by the early development of AD by the age of 60 and, although the two conditions present the same pathological hallmarks and share the alteration of many molecular mechanisms driving brain degeneration, no evidence has been sought on the implication of O-GlcNAcylation in DS pathology. Our study aimed to unravel for the first time the role of protein O-GlcNacylation in DS brain alterations positing the attention of potential trisomy-related mechanisms triggering the aberrant regulation of OGT/OGA cycle. We demonstrate the disruption of O-GlcNAcylation homeostasis, as an effect of altered OGT and OGA regulatory mechanism, and confirm the relevance of O-GlcNAcylation in the appearance of AD hallmarks in the brain of a murine model of DS. Furthermore, we provide evidence for the neuroprotective effects of brain-targeted OGA inhibition. Indeed, the rescue of OGA activity was able to restore protein O-GlcNAcylation, and reduce AD-related hallmarks and decreased protein nitration, possibly as effect of induced autophagy.
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