N-AS-triggered SPMs are direct regulators of microglia in a model of Alzheimer’s disease
| العنوان: | N-AS-triggered SPMs are direct regulators of microglia in a model of Alzheimer’s disease |
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| المؤلفون: | Hee Jin Kim, Seung Hyun Kim, Cheol-Min Park, Jae-sung Bae, Ju Youn Lee, Min-Koo Choi, Min Hee Park, Eunsoo Yu, Hee Kyung Jin, Edward H. Schuchman, Seung Hoon Han, Im-Sook Song |
| المصدر: | Nature Communications, Vol 11, Iss 1, Pp 1-19 (2020) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Neuroimmunology, Anti-Inflammatory Agents, General Physics and Astronomy, Serine, chemistry.chemical_compound, Mice, 0302 clinical medicine, Sphingosine, lcsh:Science, Neurons, Multidisciplinary, Microglia, Brain, food and beverages, Acetylation, Alzheimer's disease, Recombinant Proteins, Phosphotransferases (Alcohol Group Acceptor), medicine.anatomical_structure, Acetyltransferase, medicine.symptom, Phagocytosis, Transgene, Science, Primary Cell Culture, Inflammation, Mice, Transgenic, macromolecular substances, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, 03 medical and health sciences, Acetyl Coenzyme A, Alzheimer Disease, Memory, medicine, Presenilin-1, Animals, Humans, Neuroinflammation, General Chemistry, Disease Models, Animal, 030104 developmental biology, chemistry, nervous system, Cyclooxygenase 2, Mutagenesis, lcsh:Q, Neuroscience, 030217 neurology & neurosurgery |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::782a4eb0726efb66ab89568cfe37f061Test https://doaj.org/article/3035df8592594ac98f3be370c56a59d8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....782a4eb0726efb66ab89568cfe37f061 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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