Journal
NEUROCHEMICAL RESEARCH
Volume 46, Issue 5, Pages 1291-1304Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-021-03267-4
Keywords
Microglia; Neuroinflammation; Nicotinamide phosphoribosyltransferase; FK866
Categories
Funding
- National Natural Science Foundation of China [81671273, 81171204, 30772280, 81400925, 81471148, 81771211, 81703852]
- Shanghai Municipal Education Commission of China [14YZ046]
- Shanghai Municipal Health and Family Planning Commission of China [20134049]
- Shanghai Jiao Tong University of China [YG2013MS22]
- National Eastern Tech-transfer Center [201713972877]
- Shanghai Committee of Science and Technology [17401901000]
- National Key R and D Program of China [2017YFC1310300]
- SHSMU-ION Research Center for Brain Disorders [2015NKX007]
Ask authors/readers for more resources
NAMPT could be a promising target for microglia modulation, and NAMPT inhibition may attenuate microglial inflammation.
Alleviating microglia-mediated neuroinflammation bears great promise to reduce neurodegeneration. Nicotinamide phosphoribosyltransferase (NAMPT) may exert cytokine-like effect in the brain. However, it remains unclear about role of NAMPT in microglial inflammation. Also, it remains unknown about effect of NAMPT inhibition on microglial inflammation. In the present study, we observed that FK866 (a specific noncompetitive NAMPT inhibitor) dose-dependently inhibited lipopolysaccharide (LPS)-induced proinflammatory mediator (interleukin (IL)-6, IL-1 beta, inducible nitric oxide synthase, nitric oxide and reactive species) level increase in BV2 microglia cultures. FK866 also significantly inhibited LPS-induced polarization change in microglia. Furthermore, LPS significantly increased NAMPT expression and nuclear factor kappa B (NF-kappa B) phosphorylation in microglia. FK866 significantly decreased NAMPT expression and NF-kappa B phosphorylation in LPS-treated microglia. Finally, conditioned medium from microglia cultures co-treated with FK866 and LPS significantly increased SH-SY5Y and PC12 cell viability compared with conditioned medium from microglia cultures treated with LPS alone. Our study strongly indicates that NAMPT may be a promising target for microglia modulation and NAMPT inhibition may attenuate microglial inflammation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available
Share Paper
