The rediscovery of meningeal lymphatic vessels (MLVs) has sparked research interest in their function in numerous neurological pathologies. Craniosynostosis (CS) is caused by a premature fusion of cranial sutures during development. In this issue of the JCI, Matrongolo and colleagues show that Twist1-haploinsufficient mice that develop CS exhibit raised intracranial pressure, diminished cerebrospinal fluid (CSF) outflow, and impaired paravascular CSF-brain flow; all features that were associated with MLV defects and exacerbated pathology in mouse models of Alzheimer's disease. Activation of the mechanosensor Piezo1 with Yoda1 restored MLV function and CSF perfusion in CS models and in aged mice, opening an avenue for further development of therapeutics.
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| http://dx.doi.org/10.1172/JCI176858 | DOI Listing |
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Yoda1 opens the lymphatic path for craniosynostosis therapy.
J Clin Invest
February 2024
Wihuri Research Institute, Biomedicum Helsinki, Helsinki, Finland.
The rediscovery of meningeal lymphatic vessels (MLVs) has sparked research interest in their function in numerous neurological pathologies. Craniosynostosis (CS) is caused by a premature fusion of cranial sutures during development. In this issue of the JCI, Matrongolo and colleagues show that Twist1-haploinsufficient mice that develop CS exhibit raised intracranial pressure, diminished cerebrospinal fluid (CSF) outflow, and impaired paravascular CSF-brain flow; all features that were associated with MLV defects and exacerbated pathology in mouse models of Alzheimer's disease.
View Article and Find Full Text PDFMechanosensitive piezo1 calcium channel activates connexin 43 hemichannels through PI3K signaling pathway in bone.
Cell Biosci
December 2022
Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA.
Background: Mechanical loading promotes bone formation and osteocytes are a major mechanosensory cell in the bone. Both Piezo1 channels and connexin 43 hemichannels (Cx43 HCs) in osteocytes are important players in mechanotransduction and anabolic function by mechanical loading. However, the mechanism underlying mechanotransduction involving Piezo1 channels and Cx43 HCs in osteocytes and bone remains unknown.
View Article and Find Full Text PDFYoda1's energetic footprint on Piezo1 channels and its modulation by voltage and temperature.
Proc Natl Acad Sci U S A
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Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766.
Piezo1 channels are essential mechanically activated ion channels in vertebrates. Their selective activation by the synthetic chemical activator Yoda1 opened new avenues to probe their gating mechanisms and develop novel pharmaceuticals. Yet, the nature and extent of Piezo1 functions modulated by this small molecule remain unclear.
View Article and Find Full Text PDFPiezo1 regulates shear-dependent nitric oxide production in human erythrocytes.
Am J Physiol Heart Circ Physiol
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Biorheology Research Laboratory, Menzies Health Institute Queensland, Gold Coast, Queensland, Australia.
Mature circulating red blood cells (RBCs) are classically viewed as passive participants in circulatory function, given erythroblasts eject their organelles during maturation. Endogenous production of nitric oxide (NO) and its effects are of particular significance; however, the integration between RBC sensation of the local environment and subsequent activation of mechano-sensitive signaling networks that generate NO remain poorly understood. The present study investigated endogenous NO production via the RBC-specific nitric oxide synthase isoform (RBC-NOS), connecting membrane strain with intracellular enzymatic processes.
View Article and Find Full Text PDFContribution of Oxidative Stress Induced by Sonodynamic Therapy to the Calcium Homeostasis Imbalance Enhances Macrophage Infiltration in Glioma Cells.
Cancers (Basel)
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Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
Background: To better understand the Ca overload mechanism of SDT killing gliomas, we examined the hypothesis that the early application of the mechanosensitive Ca channel Piezo1 antagonist (GsMTx4) could have a better anti-tumor effect.
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