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Park, Cheol-Min
Synthetic & Medicinal Chemistry Lab
Research Interests
  • 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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Title
N-AS-triggered SPMs are direct regulators of microglia in a model of Alzheimer’s disease
Author
Lee, Ju YounHan, Seung HoonPark, Min HeeSong, Im-SookChoi, Min-KooYu, EunsooPark, Cheol-MinKim, Hee-JinKim, Seung HyunSchuchman, Edward H.Jin, Hee KyungBae, Jae-sung
Issue Date
2020-05
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE COMMUNICATIONS, v.11, no.1
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.
URI
https://scholarworks.unist.ac.kr/handle/201301/32323
URL
https://www.nature.com/articles/s41467-020-16080-4
DOI
10.1038/s41467-020-16080-4
ISSN
2041-1723
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PHY_Journal Papers
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