Other
13 Authors
- Chun-Yan W,
- Yan L,
- Minghong W,
- Qi Z,
- Xiangxiang Z,
- Yufei G,
- Ping S,
- Le K,
- Fei-Tong J,
- Yi-Bin W,
- Ye X,
- Xiang L,
- Bing Y
| First Author | Yi-Bin W | Year | 2022 |
| Journal | Cell Death Dis | Volume | 13 |
| Issue | 4 | Pages | 318 |
| PubMed ID | 35393391 | Mgi Jnum | J:323940 |
| Mgi Id | MGI:7263495 | Doi | 10.1038/s41419-022-04765-1 |
| Citation | Yi-Bin W, et al. (2022) Inhibition of the CEBPbeta-NFkappaB interaction by nanocarrier-packaged Carnosic acid ameliorates glia-mediated neuroinflammation and improves cognitive function in an Alzheimer's disease model. Cell Death Dis 13(4):318 |
| abstractText | Neuroinflammation occurs early in Alzheimer's disease (AD). The initial stage of AD is related to glial dysfunction, which contributes to impairment of Abeta clearance and disruption of synaptic connection. CEBPbeta, a member of the CCAAT-enhancer-binding protein (CEBP) family, modulates the expression of inflammation-associated genes, and its expression is elevated in brains undergoing degeneration and injured brains. However, the mechanism underlying CEBPbeta-mediated chronic inflammation in AD is unclear. In this study, we observed that increases in the levels of nuclear CEBPbeta facilitated the interaction of CEBPbeta with the NFkappaB p65 subunit, increasing the transcription of proinflammatory cytokines in the APP/PS1 mouse brain. Oral administration of nanocarrier-packaged carnosic acid (CA) reduced the aberrant activation of microglia and astrocytes and diminished mature IL-1beta, TNFalpha and IL-6 production in the APP/PS1 mouse brain. CA administration reduced beta-amyloid (Abeta) deposition and ameliorated cognitive impairment in APP/PS1 mice. We observed that CA blocked the interaction of CEBPbeta with NFkappaB p65, and chromatin immunoprecipitation revealed that CA reduced the transcription of the NFkappaB target genes TNFalpha and IL-6. We confirmed that CA alleviated inflammatory mediator-induced neuronal degeneration and reduced Abeta secretion by inhibiting the CEBPbeta-NFkappaB signalling pathway in vitro. Sulfobutyl ether-beta-cyclodextrin (SBEbetaCD) was used as the encapsulation agent for the CA-loaded nanocarrier to overcome the poor water solubility and enhance the brain bioavailability of CA. The CA nanoparticles (NPs) had no obvious toxicity. We demonstrated a feasible SBEbetaCD-based nanodelivery system targeting the brain. Our data provide experimental evidence that CA-loaded NPs are potential therapeutic agents for AD treatment. |
