| First Author | Li Y | Year | 2022 |
| Journal | Neuroscience | Volume | 484 |
| Pages | 140-150 | PubMed ID | 35058089 |
| Mgi Jnum | J:322651 | Mgi Id | MGI:6885478 |
| Doi | 10.1016/j.neuroscience.2021.11.001 | Citation | Li Y, et al. (2022) Etanercept Reduces Neuron Injury and Neuroinflammation via Inactivating c-Jun N-terminal Kinase and Nuclear Factor-kappaB Pathways in Alzheimer's Disease: An In Vitro and In Vivo Investigation. Neuroscience 484:140-150 |
| abstractText | Inflammation contributes to amyloid beta (Abeta) aggregation and neuron loss in Alzheimer's disease (AD). Meanwhile, tumor necrosis factor-alpha (TNF-alpha) inhibitors present strong effect on suppressing inflammation. Thus, this study aimed to investigated the effect and molecular mechanism of etanercept (ETN) (a commonly used TNF-alpha inhibitor) on neuron injury and neuroinflammation in AD. AD cellular model was constructed by co-culture of primary embryonic neuron cells and microglial cells, followed by Abeta treatment. Subsequently, ETN was used to treat AD cellular model. Besides, APPswe/PS1M146V/tauP301L transgenic (AD) mice were respectively treated with saline or ETN by intravenous injection once per 3 days for 10 times. In vitro data revealed that cell viability and neurite outgrowth were increased, but apoptosis and levels of pro-inflammatory cytokines (including TNF-alpha, interleukin-1beta, Interleukin-6 and C-C motif chemokine ligand 2 (CCL2)) were decreased by ETN treatment in AD cellular model. In vivo experiments found that ETN treatment improved spatial, long-term memory (reflected by Morrison water maze) and working memory (reflected by Y maze) in AD mice. Besides, ETN treatment reduced neuron injury (reflected by Hematoxylin-Eosin (HE) and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assays) and levels of pro-inflammatory cytokines (including TNF-alpha, interleukin-1beta, Interleukin-6 and CCL2) in AD mice. Moreover, ETN repressed the activation of c-Jun N-terminal kinase (JNK) and nuclear factor-kappaB (NF-kappaB) pathways in AD both in vitro and in vivo. In conclusion, ETN exerts neuroprotective function via inactivating JNK and NF-kappaB pathways in AD, indicating the potential of ETN for improving AD management. |
