Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김희진 | - |
dc.date.accessioned | 2019-12-09T18:07:11Z | - |
dc.date.available | 2019-12-09T18:07:11Z | - |
dc.date.issued | 2018-10 | - |
dc.identifier.citation | NEURON, v. 100, no. 1, page. 167-182.e9 | en_US |
dc.identifier.issn | 0896-6273 | - |
dc.identifier.issn | 1097-4199 | - |
dc.identifier.uri | https://www.cell.com/neuron/fulltext/S0896-6273(18)30783-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0896627318307839%3Fshowall%3Dtrue | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/120327 | - |
dc.description.abstract | 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. | en_US |
dc.description.sponsorship | This work was supported by National Research Foundation (NRF) grants funded by the Korea government (MSIT) (2017R1A2A1A17069686 and 2017R1A4A1015652). This research was also supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C2131). | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | CELL PRESS | en_US |
dc.subject | BLOOD-BRAIN-BARRIER | en_US |
dc.subject | ACID SPHINGOMYELINASE/CERAMIDE PATHWAY | en_US |
dc.subject | CAVEOLAE-MEDIATED TRANSCYTOSIS | en_US |
dc.subject | ALZHEIMERS-DISEASE | en_US |
dc.subject | PERMEABILITY | en_US |
dc.subject | CELLS | en_US |
dc.subject | CYTOSKELETON | en_US |
dc.subject | DYSFUNCTION | en_US |
dc.subject | DISRUPTION | en_US |
dc.subject | MECHANISMS | en_US |
dc.title | Vascular and Neurogenic Rejuvenation in Aging Mice by Modulation of ASM | en_US |
dc.type | Article | en_US |
dc.relation.no | 1 | - |
dc.relation.volume | 100 | - |
dc.identifier.doi | 10.1016/j.neuron.2018.09.010 | - |
dc.relation.page | 167-167 | - |
dc.relation.journal | NEURON | - |
dc.contributor.googleauthor | Park, Min Hee | - |
dc.contributor.googleauthor | Lee, Ju Youn | - |
dc.contributor.googleauthor | Park, Kang Ho | - |
dc.contributor.googleauthor | Jung, In Kyung | - |
dc.contributor.googleauthor | Kim, Kyoung-Tae | - |
dc.contributor.googleauthor | Lee, Yong-Seok | - |
dc.contributor.googleauthor | Ryu, Hyun-Hee | - |
dc.contributor.googleauthor | Jeong, Yong | - |
dc.contributor.googleauthor | Kang, Minseok | - |
dc.contributor.googleauthor | Kim, Hee Jin | - |
dc.relation.code | 2018001309 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | hyumcbrain | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.