ArticleScientific reports2020
Small molecule activation of metabolic enzyme pyruvate kinase muscle isozyme 2, PKM2, circumvents photoreceptor apoptosis.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Neuroprotective Agents for Photoreceptor Rescue Following Experimental Retinal Detachment in Rodents: A Systematic Review.Investigative ophthalmology & visual science · 2026Pooled it
- Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress.Redox biology · 2026Article
- Interdependent roles of PKM2 in photoreceptors and RPE: implications for retinal degeneration.Cell death & disease · 2026Article
- Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress.bioRxiv : the preprint server for biology · 2026Article
- Review
- Pyruvate kinase M2 in Alzheimer's disease: from dysregulation to therapeutic inhibition.Brain communications · 2026Review
- Metabolism, a Blossoming Target for Small-Molecule Anticancer Drugs.Molecules (Basel, Switzerland) · 2025Review
- A Novel, Long-Acting, Small Molecule PKM2 Activator and Its Potential Broad Application Against Photoreceptor Degeneration.Translational vision science & technology · 2025Article
- Article
- PKM2 regulates osteoclastogenesis by affecting osteoclast precursor cell fusion via downregulation of OC-STAMP and DC-STAMP.The Journal of biological chemistry · 2025Article
- Emerging Targets, Novel Directions, and Innovative Approaches in Thrombosis Therapy.Aging and disease · 2025Review
- Article
- IGF-1 Signaling Modulates Oxidative Metabolism and Stress Resistance in ARPE-19 Cells Through PKM2 Function.International journal of molecular sciences · 2024Article
- Age-Related Changes in the Glycolytic Enzymes of M2-Isoform of Pyruvate Kinase and Fructose-1,6-Bisphosphate Aldolase: Implications to Age-Related Macular Degeneration.Aging and disease · 2024Article
- Reinventing the Penumbra - the Emerging Clockwork of a Multi-modal Mechanistic Paradigm.Translational stroke research · 2023Review
- Article
- Flow cytometric method for the detection and quantification of retinal cell death and oxidative stress.Experimental eye research · 2023Article
- Development of Novel Small-Molecule Activators of Pyruvate Kinase Muscle Isozyme 2, PKM2, to Reduce Photoreceptor Apoptosis.Pharmaceuticals (Basel, Switzerland) · 2023Article
- IgSF11-mediated phosphorylation of pyruvate kinase M2 regulates osteoclast differentiation and prevents pathological bone loss.Bone research · 2023Article
- Rod photoreceptor-specific deletion of cytosolic aspartate aminotransferase, GOT1, causes retinal degeneration.Frontiers in ophthalmology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Photoreceptor cell death is the ultimate cause of vision loss in many retinal disorders, and there is an unmet need for neuroprotective modalities to improve photoreceptor survival. Similar to cancer cells, photoreceptors maintain pyruvate kinase muscle isoform 2 (PKM2) expression, which is a critical regulator in aerobic glycolysis. Unlike PKM1, which has constitutively high catalytic activity, PKM2 is under complex regulation. Recently, we demonstrated that genetically reprogramming photoreceptor metabolism via PKM2-to-PKM1 substitution is a promising neuroprotective strategy. Here, we explored the neuroprotective effects of pharmacologically activating PKM2 via ML-265, a small molecule activator of PKM2, during acute outer retinal stress. We found that ML-265 increased PKM2 activity in 661 W cells and in vivo in rat eyes without affecting the expression of genes involved in glucose metabolism. ML-265 treatment did, however, alter metabolic intermediates of glucose metabolism and those necessary for biosynthesis in cultured cells. Long-term exposure to ML-265 did not result in decreased photoreceptor function or survival under baseline conditions. Notably, though, ML-265-treatment did reduce entrance into the apoptotic cascade in in vitro and in vivo models of outer retinal stress. These data suggest that reprogramming metabolism via activation of PKM2 is a novel, and promising, therapeutic strategy for photoreceptor neuroprotection.
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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.