ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2013
PHLPP1 gene deletion protects the brain from ischemic injury.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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.
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- PHLPP is neither a Phosphatase nor a Tumor Suppressor.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Genetic correlation analysis of Alzheimer's disease and stroke implicates PHLPP1 as a shared locus in individuals of African ancestry.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Local genetic correlation analysis of Alzheimer's disease and stroke implicatesmedRxiv : the preprint server for health sciences · 2025Article
- PHLPP1 deficiency alleviates dopaminergic neurodegeneration and represses neuroinflammation in Parkinson's disease.Behavioral and brain functions : BBF · 2025Article
- PHLPP1 regulates region-specific astroglial mitochondrial fission in response to oxidative stress in the male rat hippocampus.Scientific reports · 2025Article
- PHLPP2 is a pseudophosphatase that lost activity in the metazoan ancestor.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Postnatal deletion of Phlpp1 in chondrocytes delays post-traumatic osteoarthritis in male mice.Osteoarthritis and cartilage open · 2025Article
- CPR: cardiac phosphatase in resuscitation.The Journal of clinical investigation · 2023Article
- A cell-penetrating PHLPP peptide improves cardiac arrest survival in murine and swine models.The Journal of clinical investigation · 2023Article
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- PHLPP isoforms differentially regulate Akt isoforms and AS160 affecting neuronal insulin signaling and insulin resistance via Scribble.Cell communication and signaling : CCS · 2022Article
- PHLPP Inhibitor NSC74429 Is Neuroprotective in Rodent Models of Cardiac Arrest and Traumatic Brain Injury.Biomolecules · 2022Article
- Mesenchymal Stem Cell-Derived Extracellular Vesicles as Proposed Therapy in a Rat Model of Cerebral Small Vessel Disease.International journal of molecular sciences · 2022Article
- Protective potential of hydroxysafflor yellow A in cerebral ischemia and reperfusion injury: An overview of evidence from experimental studies.Frontiers in pharmacology · 2022Review
- On the PHLPPside: Emerging roles of PHLPP phosphatases in the heart.Cellular signalling · 2021Review
- Metal dependent protein phosphatase PPM family in cardiac health and diseases.Cellular signalling · 2021Review
- Chondrocytic and pharmacokinetic properties of Phlpp inhibitors.Osteoarthritis and cartilage open · 2021Article
- Inhibition of PHLPP1/2 phosphatases rescues pancreatic β-cells in diabetes.Cell reports · 2021Article
- Pleckstrin homology (PH) domain and Leucine Rich Repeat Phosphatase 1 (Phlpp1) Suppresses Parathyroid Hormone Receptor 1 (Pth1r) Expression and Signaling During Bone Growth.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
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Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
A recently discovered protein phosphatase PHLPP (PH domain Leucine-rich repeat Protein Phosphatase) has been shown to dephosphorylate Akt on its hydrophobic motif (Ser473) thereby decreasing Akt kinase activity. We generated PHLPP1 knockout (KO) mice and used them to explore the ability of enhanced in vivo Akt signaling to protect the brain against ischemic insult. Brains from KO mice subjected to middle cerebral artery occlusion (MCAO) for 2 hours showed significantly greater increases in Akt activity and less neurovascular damage after reperfusion than wild-type (WT) mice. Remarkably, infarct volume in the PHLPP1 KO was significantly reduced compared with WT (12.7±2.7% versus 22.9±3.1%) and this was prevented by Akt inhibition. Astrocytes from KO mice and neurons in which PHLPP1 was downregulated showed enhanced Akt activation and diminished cell death in response to oxygen-glucose deprivation. Thus, deletion of PHLPP1 can enhance Akt activation in neurons and astrocytes, and can significantly increase cell survival and diminish infarct size after MCAO. Inhibition of PHLPP could be a therapeutic approach to minimize damage after focal ischemia.
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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.