ArticleCell metabolism2022
Warburg-like metabolic transformation underlies neuronal degeneration in sporadic Alzheimer's disease.
Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 2 of them syntheses that pooled it.
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Who cites it
116 citing papers in PubMed, 2 syntheses or guidelines pooled it, 167 citations in OpenAlex.
- Multi-omics and high-spatial-resolution omics: deciphering complexity in neurological disorders.GigaScience · 2025Pooled it
- Direct Conversion of Fibroblast into Neurons for Alzheimer's Disease Research: A Systematic Review.Journal of Alzheimer's disease : JAD · 2023Pooled it
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- ZBP1-mediated Treg cell dysfunction exacerbates neuroimmune dysregulation in Alzheimer's disease under metabolic stress.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Reduced expression of Brain Expressed X-linked genes in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Article
- Histone H4 lysine 12 lactylation-driven ZIP14 expression is involved in electroacupuncture therapy against cerebral ischemia/reperfusion injury in mice.Journal of advanced research · 2026Article
- Transaldolase 1 contributes to pentose phosphate pathway disruption and synaptic dysfunction in Alzheimer's disease.Translational neurodegeneration · 2026Article
- Cortistatin as a modulator of inflammatory and mitochondrial dysfunction in Huntington´s disease.Journal of neuroinflammation · 2026Article
- Circadian transcriptomic disruptions in the hippocampus precede cognitive deficits in a mouse model of Alzheimer's disease.Neural regeneration research · 2026Article
- Aerobic glycolysis in Schizophrenia: Developmental rescue or energetic breakdown?Molecular psychiatry · 2026Review
- Sex differences in brain glucose metabolism and Alzheimer's disease risk and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Upregulated PKM2 Protects Dopaminergic Neurons From Oxidative Damage Through Nrf2 Transactivation in an MPTP-Induced Mouse Model of Parkinson's Disease.CNS neuroscience & therapeutics · 2026Article
- Glycolysis: The Bridge Between Cellular Interaction and Alzheimer's Disease.Biomolecules · 2026Review
- Acarbose modulates microglial Pkm2 acetylation to reshape immunometabolism and preserve retinal neurons after ischemia-reperfusion.Journal of neuroinflammation · 2026Article
- Exosomes derived from human umbilical cord mesenchymal stem cells attenuate neuroinflammation in intracerebral hemorrhage rats by modulating lactylation modification.Journal of translational medicine · 2026Article
- Establishment and validation of an Alzheimer's disease diagnostic model on the basis of exhaled volatile organic compound characteristics.Translational psychiatry · 2026Article
- Metabolic trajectories in developing human neocortical neurons.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A novel PGK1 activator improves Alzheimer's disease by regulating glycolysis.Alzheimer's research & therapy · 2026Article
- Spatiotemporal transcriptomic profiling reveals upregulation of glycolysis pathway genes before overt tauopathy in the PS19 mouse model.Experimental & molecular medicine · 2026Article
- Analyses of astrocyte-neuron lactate shuttle transporter levels in brain tissues from people with HIV-associated neurocognitive impairment and Alzheimer's disease.NeuroImmune pharmacology and therapeutics · 2026Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
The drivers of sporadic Alzheimer's disease (AD) remain incompletely understood. Utilizing directly converted induced neurons (iNs) from AD-patient-derived fibroblasts, we identified a metabolic switch to aerobic glycolysis in AD iNs. Pathological isoform switching of the glycolytic enzyme pyruvate kinase M (PKM) toward the cancer-associated PKM2 isoform conferred metabolic and transcriptional changes in AD iNs. These alterations occurred via PKM2's lack of metabolic activity and via nuclear translocation and association with STAT3 and HIF1α to promote neuronal fate loss and vulnerability. Chemical modulation of PKM2 prevented nuclear translocation, restored a mature neuronal metabolism, reversed AD-specific gene expression changes, and re-activated neuronal resilience against cell death.
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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.