Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김희진 | - |
dc.date.accessioned | 2021-11-22T07:44:30Z | - |
dc.date.available | 2021-11-22T07:44:30Z | - |
dc.date.issued | 2020-05 | - |
dc.identifier.citation | NATURE COMMUNICATIONS, v. 11, no. 1, article no. 2358 | en_US |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | https://www.nature.com/articles/s41467-020-16080-4 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/166407 | - |
dc.description.abstract | Sphingosine kinase1 (SphK1) is an acetyl-CoA dependent acetyltransferase which acts on cyclooxygenase2 (COX2) in neurons in a model of Alzheimer's disease (AD). However, the mechanism underlying this activity was unexplored. Here we show that N-acetyl sphingosine (N-AS) is first generated by acetyl-CoA and sphingosine through SphK1. N-AS then acetylates serine 565 (S565) of COX2, and the N-AS-acetylated COX2 induces the production of specialized pro-resolving mediators (SPMs). In a mouse model of AD, microglia show a reduction in N-AS generation, leading to decreased acetyl-S565 COX2 and SPM production. Treatment with N-AS increases acetylated COX2 and N-AS-triggered SPMs in microglia of AD mice, leading to resolution of neuroinflammation, an increase in microglial phagocytosis, and improved memory. Taken together, these results identify a role of N-AS in the dysfunction of microglia in AD. Neuronal sphingosine kinase 1 (SphK1) acetylates COX2 which is needed for microglial phagocytosis activity, and release of pro-resolving mediators (SPMs) from neurons. Here the authors examine how SphK1-mediates COX2 acetylation, and how this leads to increased secretion of SPMs from neurons in the context of Alzheimer's disease models. | en_US |
dc.description.sponsorship | This research was supported by the Basic Science Research Program (2017R1A4A1015652, 2020R1A2C3006875) and the Original Technology Research Program for Brain Science (2018M3C7A1056513) of the NRF funded by the Korean government, MSIT. This research was also supported by a grant of the Korea Health Technology R&D Project through the KHIDI, funded by the Ministry of Health & Welfare, Republic of Korea (HI16C2131) and Research Fund (1.180002.01) of UNIST. | en_US |
dc.language.iso | en | en_US |
dc.publisher | NATURE PUBLISHING GROUP | en_US |
dc.subject | RESOLVING LIPID MEDIATORS | en_US |
dc.subject | INFLAMMATION | en_US |
dc.subject | RESOLUTION | en_US |
dc.subject | POLARIZATION | en_US |
dc.subject | PATHOLOGY | en_US |
dc.subject | PROTEIN | en_US |
dc.subject | NAIVE | en_US |
dc.title | N-AS-triggered SPMs are direct regulators of microglia in a model of Alzheimer's disease | en_US |
dc.type | Article | en_US |
dc.relation.no | 1 | - |
dc.relation.volume | 11 | - |
dc.identifier.doi | 10.1038/s41467-020-16080-4 | - |
dc.relation.page | 1-19 | - |
dc.relation.journal | NATURE COMMUNICATIONS | - |
dc.contributor.googleauthor | Lee, Ju Youn | - |
dc.contributor.googleauthor | Han, Seung Hoon | - |
dc.contributor.googleauthor | Park, Min Hee | - |
dc.contributor.googleauthor | Song, Im-Sook | - |
dc.contributor.googleauthor | Choi, Min-Koo | - |
dc.contributor.googleauthor | Yu, Eunsoo | - |
dc.contributor.googleauthor | Park, Cheol-Min | - |
dc.contributor.googleauthor | Kim, Hee-Jin | - |
dc.contributor.googleauthor | Kim, Seung Hyun | - |
dc.contributor.googleauthor | Schuchman, Edward H. | - |
dc.relation.code | 2020046258 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | hyumcbrain | - |
dc.identifier.researcherID | P-1903-2015 | - |
dc.identifier.orcid | https://orcid.org/0000-0001-7880-690X | - |
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