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The dual role of PGAM5 in inflammation - Nature
...This proinflammatory phenotype may be mediated by the PGAM5-dependent inhibition of oxeiptosis, necroptosis and apoptosis, as well as the non-PGAM5-dependent activation of programmed cell......
https://www.nature.com/articles/s12276-025-01391-7
A novel PGAM5 inhibitor LFHP-1c protects blood-brain barrier ... - PubMed
...Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear ......
https://pubmed.ncbi.nlm.nih.gov/34386325/
Physiological and pathological roles of PGAM5: An update and future ...
...The inhibition of miR-330 leads to the activation of PGAM5-mediated mitophagy, which is linked to reduced cerebral infarction, edema, mortality, and apoptosis following 6-hour of permanent middle cerebral artery occlusion. 75 Notably, a different investigation demonstrated that PGAM5 inhibition by compound LFHP-1c effectively improved the ......
https://www.cell.com/iscience/fulltext/S2589-0042(24)02766-4
Mitochondrial Protein PGAM5 Emerges as a New Regulator in Neurological ...
...Knockdown of PGAM5 or NRF2 released KEAP1 from complex to interact with cullin-3, a scaffold protein for E3 ubiquitin ligase complex, and subsequently mediated degradation of Miro2, leading to inhibition of mitochondrial retrograde trafficking....
https://pmc.ncbi.nlm.nih.gov/articles/PMC8496500/
What is PGAM5 and Its Role in Health and Disease?
...By dephosphorylating target proteins, PGAM5 can alter their activity, location, or stability, influencing a range of cellular processes. One process regulated by PGAM5 is mitochondrial dynamics, which involves the continuous fission (splitting) and fusion (joining) of mitochondria....
https://biologyinsights.com/what-is-pgam5-and-its-role-in-health-and-disease/
A novel PGAM5 inhibitor LFHP-1c protects blood?brain barrier integrity ...
...LFHP-1c directly binding to PGAM5 inhibits PGAM5 enzyme activity and impairs PGAM5 interaction with NRF2, promoting NRF2 transcription activity to protect against blood?brain barrier disruption and ischemic brain injury....
https://www.sciencedirect.com/science/article/pii/S2211383521000101
Inhibition of PGAM5 hyperactivation reduces neuronal apoptosis in PC12 ...
...Phosphoglycerate translocase 5 (PGAM5), as a crossroads of multiple signaling pathways, can lead to mitochondrial fission, which in turn triggers the onset and development of necroptosis, and thus PGAM5 may be a novel target for the prevention and treatment of vascular dementia....
https://pubmed.ncbi.nlm.nih.gov/39754994/
PGAM5 is a key driver of mitochondrial dysfunction in experimental lung ...
...Our study identifies PGAM5 as an important regulator of mitochondrial homeostasis in pulmonary fibrosis. Our data further indicate PGAM5-mediated mitophagy itself as a pivotal gateway event in the mediation of self-sustaining mitochondrial damage and membrane depolarization....
https://pmc.ncbi.nlm.nih.gov/articles/PMC11105634/
Unveiling the PGAM5-ANGPTL3 Axis: Implications for Atherosclerosis ...
...Inhibition of RIPK3 phosphorylation with a chemical inhibitor reduces PGAM5 expression and mitigates macrophage activation, thereby alleviating atherosclerosis in mouse models. Gene expression analysis of PGAM5-deficient human macrophages identified ANGPTL3 as 1 of 6 highly up-regulated genes....
https://www.jacc.org/doi/10.1016/j.jacbts.2025.02.023
Inhibition of Phosphoglycerate Mutase 5 Reduces Necroptosis in Rat ...
...Inhibition of PGAM5 can reduce necroptosis in I/R-treated rat hearts through suppression of Drp1; there is a positive feedback between RIPK1 and PGAM5, and PGAM5 might serve as a novel therapeutic target for prevention of myocardial I/R injury....
https://link.springer.com/article/10.1007/s10557-018-06848-8
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