Although many reports have revealed dysfunction of endothelial cells in aging, resulting in blood-brain barrier (BBB) breakdown, the underlying mechanism or mechanisms remain to be explored. Here, we find that acid sphingomyelinase (ASM) is a critical factor for regulating brain endothelial barrier integrity. ASM is increased in brain endothelium and/or plasma of aged humans and aged mice, leading to BBB disruption by increasing caveolae-mediated transcytosis. Genetic inhibition and endothelial-specific knockdown of ASM in mice ameliorated BBB breakdown and neurocognitive impairment during aging. Using primary mouse brain endothelial cells, we found that ASM regulated the caveolae-cytoskeleton interaction through protein phosphatase 1-mediated ezrin/radixin/moesin (ERM) dephosphorylation and apoptosis. Moreover, mice with conditional ASM overexpression in brain endothelium accelerated significant BBB impairment and neurodegenerative change. Overall, these results reveal a novel role for ASM in the control of neurovascular function in aging, suggesting that ASM may represent a new therapeutic target for anti-aging.
Pubmed ID: 30269989 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets P-glycoprotein 1
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets donkey anti-goat IgG-HRP
View all literature mentionsThis polyclonal targets Mouse IgG
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis polyclonal targets ACTG1, ACTC1, ACTA1, ACTA2, ACTG2, ACTB
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgM (?? chain)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis monoclonal targets Bcl-2 (D17C4) Rabbit mAb (Mouse Preferred)
View all literature mentionsThis monoclonal targets p53 (1C12) Mouse mAb
View all literature mentionsThis monoclonal targets Akt (pan) (C67E7) Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis unknown targets Ezrin / Radixin / Moesin
View all literature mentionsThis monoclonal targets Ezrin, phospho (Thr567) / Radixin, phospho (Thr564) / Moesin, phospho (Thr558)
View all literature mentionsThis polyclonal targets Ezr
View all literature mentionsThis unknown targets Mouse
View all literature mentionsThis monoclonal targets Human SMPD1 MAb (Clone 563418)
View all literature mentionsThis monoclonal targets Rab7
View all literature mentionsThis monoclonal targets Rab5
View all literature mentionsThis monoclonal targets P Glycoprotein
View all literature mentionsThis monoclonal targets BCRP/ABCG2
View all literature mentionsThis polyclonal targets LAMP1
View all literature mentionsThis monoclonal targets Caveolin 1
View all literature mentionsThis polyclonal targets Human VE Cadherin
View all literature mentionsThis monoclonal targets Claudin 5
View all literature mentionsThis monoclonal targets β-Catenin
View all literature mentionsThis monoclonal targets OCCLUDIN
View all literature mentionsThis polyclonal targets ZO-1
View all literature mentionsThis polyclonal targets NG2 Chondroitin Sulfate Proteoglycan
View all literature mentionsThis polyclonal targets Mouse Laminin alpha 4
View all literature mentionsThis monoclonal targets Syp
View all literature mentionsThis monoclonal targets Glucose Transporter GLUT1 antibody [EPR3915]
View all literature mentionsThis polyclonal targets ABCG2
View all literature mentionsThis unknown targets rabbit IgG
View all literature mentionsThis monoclonal targets Caveolin-1
View all literature mentionsThis polyclonal targets Human EHD2
View all literature mentionsThis polyclonal targets Mouse PTRF
View all literature mentionsThis polyclonal targets Caveolin
View all literature mentionsThis monoclonal targets Caveolin (pY14)
View all literature mentionsThis polyclonal targets Thrombin HC
View all literature mentionsThis polyclonal targets Human Fibrinogen
View all literature mentionsThis polyclonal targets Collagen IV
View all literature mentionsThis polyclonal targets Caspase 3 active (cleaved) form
View all literature mentionsThis monoclonal targets Actin, alpha, Smooth Muscle
View all literature mentionsThis monoclonal targets PDGF Receptor beta
View all literature mentionsThis polyclonal targets Human Acid sphingomyelinase
View all literature mentionsThis monoclonal targets CD31
View all literature mentionsThis monoclonal targets CD31
View all literature mentionsThis monoclonal targets TUBB2A
View all literature mentionsThis polyclonal targets Rabbit Glial Fibrillary Acidic Protein (GFAP)
View all literature mentionsThis polyclonal targets CD31/PECAM-1
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware tool for automated microscope acquisition, device control, and image analysis. Used for integrating dissimilar fluorescent microscope hardware and peripherals into a single custom workstation, while providing all the tools needed to perform analysis of acquired images. Offers user friendly application modules for analysis such as cell signaling, cell counting, and protein expression.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsMus musculus with name STOCK Cav1tm1Mls/J from IMSR.
View all literature mentionsThis monoclonal targets P-glycoprotein 1
View all literature mentions