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Park, Cheol-Min
Synthetic & Medicinal Chemistry Lab
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  • Organic synthesis, medicinal chemistry, chemical biology

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N-AS-triggered SPMs are direct regulators of microglia in a model of Alzheimer’s disease

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dc.contributor.author Lee, Ju Youn ko
dc.contributor.author Han, Seung Hoon ko
dc.contributor.author Park, Min Hee ko
dc.contributor.author Song, Im-Sook ko
dc.contributor.author Choi, Min-Koo ko
dc.contributor.author Yu, Eunsoo ko
dc.contributor.author Park, Cheol-Min ko
dc.contributor.author Kim, Hee-Jin ko
dc.contributor.author Kim, Seung Hyun ko
dc.contributor.author Schuchman, Edward H. ko
dc.contributor.author Jin, Hee Kyung ko
dc.contributor.author Bae, Jae-sung ko
dc.date.available 2020-06-08T01:40:00Z -
dc.date.created 2020-06-05 ko
dc.date.issued 2020-05 ko
dc.identifier.citation NATURE COMMUNICATIONS, v.11, no.1 ko
dc.identifier.issn 2041-1723 ko
dc.identifier.uri https://scholarworks.unist.ac.kr/handle/201301/32323 -
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. ko
dc.language 영어 ko
dc.publisher NATURE PUBLISHING GROUP ko
dc.title N-AS-triggered SPMs are direct regulators of microglia in a model of Alzheimer’s disease ko
dc.type ARTICLE ko
dc.identifier.scopusid 2-s2.0-85084501724 ko
dc.identifier.wosid 000537248100001 ko
dc.type.rims ART ko
dc.identifier.doi 10.1038/s41467-020-16080-4 ko
dc.identifier.url https://www.nature.com/articles/s41467-020-16080-4 ko
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