Vascular and Neurogenic Rejuvenation in Aging Mice by Modulation of ASM

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dc.contributor.authorPark, Min Heeko
dc.contributor.authorLee, Ju Younko
dc.contributor.authorPark, Kang Hoko
dc.contributor.authorJung, In Kyungko
dc.contributor.authorKim, Kyoung-Taeko
dc.contributor.authorLee, Yong-Seokko
dc.contributor.authorRyu, Hyun-Heeko
dc.contributor.authorJeong, Yongko
dc.contributor.authorKang, Minseokko
dc.contributor.authorSchwaninger, Markusko
dc.contributor.authorGulbins, Erichko
dc.contributor.authorReichel, Martinko
dc.contributor.authorKornhuber, Johannesko
dc.contributor.authorYamaguchi, Tomoyukiko
dc.contributor.authorKim, Hee Jinko
dc.contributor.authorKim, Seung Hyunko
dc.contributor.authorSchuchman, Edward H.ko
dc.contributor.authorJin, Hee Kyungko
dc.contributor.authorBae, Jae-Sungko
dc.date.accessioned2018-11-12T04:50:53Z-
dc.date.available2018-11-12T04:50:53Z-
dc.date.created2018-10-29-
dc.date.created2018-10-29-
dc.date.created2018-10-29-
dc.date.issued2018-10-
dc.identifier.citationNEURON, v.100, no.1, pp.167 - +-
dc.identifier.issn0896-6273-
dc.identifier.urihttp://hdl.handle.net/10203/246547-
dc.description.abstractAlthough 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.-
dc.languageEnglish-
dc.publisherCELL PRESS-
dc.titleVascular and Neurogenic Rejuvenation in Aging Mice by Modulation of ASM-
dc.typeArticle-
dc.identifier.wosid000446862000018-
dc.identifier.scopusid2-s2.0-85054143700-
dc.type.rimsART-
dc.citation.volume100-
dc.citation.issue1-
dc.citation.beginningpage167-
dc.citation.endingpage+-
dc.citation.publicationnameNEURON-
dc.identifier.doi10.1016/j.neuron.2018.09.010-
dc.contributor.localauthorJeong, Yong-
dc.contributor.nonIdAuthorPark, Min Hee-
dc.contributor.nonIdAuthorLee, Ju Youn-
dc.contributor.nonIdAuthorPark, Kang Ho-
dc.contributor.nonIdAuthorJung, In Kyung-
dc.contributor.nonIdAuthorKim, Kyoung-Tae-
dc.contributor.nonIdAuthorLee, Yong-Seok-
dc.contributor.nonIdAuthorRyu, Hyun-Hee-
dc.contributor.nonIdAuthorSchwaninger, Markus-
dc.contributor.nonIdAuthorGulbins, Erich-
dc.contributor.nonIdAuthorReichel, Martin-
dc.contributor.nonIdAuthorKornhuber, Johannes-
dc.contributor.nonIdAuthorYamaguchi, Tomoyuki-
dc.contributor.nonIdAuthorKim, Hee Jin-
dc.contributor.nonIdAuthorKim, Seung Hyun-
dc.contributor.nonIdAuthorSchuchman, Edward H.-
dc.contributor.nonIdAuthorJin, Hee Kyung-
dc.contributor.nonIdAuthorBae, Jae-Sung-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordPlusBLOOD-BRAIN-BARRIER-
dc.subject.keywordPlusACID SPHINGOMYELINASE/CERAMIDE PATHWAY-
dc.subject.keywordPlusCAVEOLAE-MEDIATED TRANSCYTOSIS-
dc.subject.keywordPlusALZHEIMERS-DISEASE-
dc.subject.keywordPlusPERMEABILITY-
dc.subject.keywordPlusCELLS-
dc.subject.keywordPlusCYTOSKELETON-
dc.subject.keywordPlusDYSFUNCTION-
dc.subject.keywordPlusDISRUPTION-
dc.subject.keywordPlusMECHANISMS-
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