한빛사논문
- 조회576
Hyung-lok Chung,1,2,3,7,8,9,* Qi Ye,2,4,7 Ye-Jin Park,1,2 Zhongyuan Zuo,1 Jung-Wan Mok,1,2 Oguz Kanca,1,2 Sudhir Gopal Tattikota,5 Shenzhao Lu,1,2 Nobert Perrimon,5,6 Hyun Kyoung Lee,2,4,* and Hugo J. Bellen1,2,*
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
2Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
3Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA
4Department of Pediatrics, Section of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
5Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA
6Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, Boston, MA, USA
7These authors contributed equally
8Present address: Department of Neurology, Houston Methodist Research Institute, Houston, TX, USA
9Lead contact
*Correspondence: Hyung-lok Chung, Hyun Kyoung Lee and Hugo J. Bellen
Abstract
VLCFAs (very-long-chain fatty acids) are the most abundant fatty acids in myelin. Hence, during demyelination or aging, glia are exposed to higher levels of VLCFA than normal. We report that glia convert these VLCFA into sphingosine-1-phosphate (S1P) via a glial-specific S1P pathway. Excess S1P causes neuroinflammation, NF-κB activation, and macrophage infiltration into the CNS. Suppressing the function of S1P in fly glia or neurons, or administration of Fingolimod, an S1P receptor antagonist, strongly attenuates the phenotypes caused by excess VLCFAs. In contrast, elevating the VLCFA levels in glia and immune cells exacerbates these phenotypes. Elevated VLCFA and S1P are also toxic in vertebrates based on a mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). Indeed, reducing VLCFA with bezafibrate ameliorates the phenotypes. Moreover, simultaneous use of bezafibrate and fingolimod synergizes to improve EAE, suggesting that lowering VLCFA and S1P is a treatment avenue for MS.
논문정보
- Research article
- 2023년 04월 (BRIC 등록일 2023-04-21)
- 국외 연구진
- 의약학 > 신경의학
관련 웨비나
![Rare to common diseases: Role of lipid metabolism in neuroinflammation [Cell Metab.]](/upload/board/files/onseminar/thumb/thumb_0000566.png)
학술웨비나
Rare to common diseases: Role of lipid metabolism in neuroinflammation [Cell Metab.] More than 300 million patients are estimated worldwide with a rare genetic disease. Unfortunately, many of these patients remain undiagnosed for many years. Drosophila is now playing a critical role in discovering rare human genetic disorders based on collaborations with clinicians and human geneticists worldwide. I will show how we discovered new human diseases, tackled pathogenic mechanisms and screened existing drugs for therapeutic purposes using a fly model.- 정형록(HOUSTON METHODIST RESEARCH INSTITUTE & Weill Cornell Medicine)
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