N-AS-triggered SPMs are direct regulators of microglia in a model of Alzheimer's disease
- Title
- N-AS-triggered SPMs are direct regulators of microglia in a model of Alzheimer's disease
- Author
- 김희진
- Keywords
- RESOLVING LIPID MEDIATORS; INFLAMMATION; RESOLUTION; POLARIZATION; PATHOLOGY; PROTEIN; NAIVE
- Issue Date
- 2020-05
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE COMMUNICATIONS, v. 11, no. 1, article no. 2358
- 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://www.nature.com/articles/s41467-020-16080-4https://repository.hanyang.ac.kr/handle/20.500.11754/166407
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-020-16080-4
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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