ArticleNature metabolism2025
Neuronal glycogen breakdown mitigates tauopathy via pentose-phosphate-pathway-mediated oxidative stress reduction.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed.
- Corpora amylacea profiling reveals disease stage and brain region-specific alterations in glycogen metabolism in Alzheimer's disease patient brains.Cell reports. Medicine · 2026Article
- Transaldolase 1 contributes to pentose phosphate pathway disruption and synaptic dysfunction in Alzheimer's disease.Translational neurodegeneration · 2026Article
- Emerging Nanoreactors for Precision Disease Treatment: From Principles to Biomedical Applications.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Peripheral metabolic dysfunction drives sleep disruption in TDP-43 proteinopathy.bioRxiv : the preprint server for biology · 2026Article
- Pentose Phosphate Pathway Is Critical for Providing Energy by Bypassing 6-Phosphofructo-1-Kinase (PFK1) During Increased Neuronal Activity.Metabolites · 2026Review
- Enriched Environment Suppresses Neuronal Ferroptosis Through SIRT1/AKT/GSK3β-Dependent Glycogen Metabolic Reprogramming After Cerebral Ischemia-Reperfusion.Antioxidants (Basel, Switzerland) · 2026Article
- Astrocytic PYGM attenuates tau pathology by promoting lactate-mediated neuroprotection.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Acetyl-CoA availability regulates neuronal metabolism, growth, and synaptic activity.bioRxiv : the preprint server for biology · 2026Article
- Metabolic cell death networks in Alzheimer's disease: mechanistic links and therapeutic perspectives of ferroptosis, cuproptosis, and disulfidptosis.Frontiers in cell and developmental biology · 2026Review
- Implications of pentose phosphate metabolism and astrocyte co-expression patterns in the pathogenesis of Alzheimer's disease: evidence from artificial intelligence-driven omics and clinical validation.Frontiers in neuroscience · 2026Article
- Genetic regulators of neuronal survival across metabolic environments.bioRxiv : the preprint server for biology · 2025Article
- Neuromodulatory control of energy reserves in dopaminergic neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Regulation of tau protein by circCwc27: shared pathogenic mechanisms in type 2 diabetes mellitus and Alzheimer's disease.Brain informatics · 2025Article
- Neuronal glycogen breakdown mitigates tauopathy via pentose-phosphate-pathway-mediated oxidative stress reduction.Nature metabolism · 2025Article
- Glioinflammation: disease-associated microglia and astrocytes in psychiatric disorders, neurodegeneration, and senescence.Frontiers in cellular neuroscience · 2025Review
Corrections and comments
- Update of
Authors and funding
19 authors.
Funding
Abstract
Tauopathies encompass a range of neurodegenerative disorders, such as Alzheimer's disease (AD) and frontotemporal lobar degeneration with tau inclusions (FTLD-tau), for which there are currently no successful treatments. Here, we show impaired glycogen metabolism in the brain of a tauopathy Drosophila melanogaster model and people with AD, indicating a link between tauopathies and glycogen metabolism. We demonstrate that the breakdown of neuronal glycogen ameliorates the tauopathy phenotypes in flies and induced pluripotent stem cell (iPSC)-derived neurons from people with FTLD-tau. Glycogen breakdown redirects glucose flux to the pentose phosphate pathway and alleviates oxidative stress. Our findings uncover a critical role for the neuroprotective effects of dietary restriction (DR) by increasing glycogen breakdown. Mechanistically, we show a potential interaction between tau protein and glycogen, suggesting a vicious cycle in which tau binding promotes glycogen accumulation in neurons, which in turn exacerbates tau accumulation which further disrupts cellular homeostasis. Our studies identify impaired glycogen metabolism as a key hallmark for tauopathies and offer a promising therapeutic target in tauopathy and other neurodegenerative diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.