| First Author | Feng X | Year | 2014 |
| Journal | Cell Death Differ | Volume | 21 |
| Issue | 3 | Pages | 397-406 |
| PubMed ID | 24162663 | Mgi Jnum | J:229071 |
| Mgi Id | MGI:5750295 | Doi | 10.1038/cdd.2013.152 |
| Citation | Feng X, et al. (2014) beta-arrestin protects neurons by mediating endogenous opioid arrest of inflammatory microglia. Cell Death Differ 21(3):397-406 |
| abstractText | Microglial activation worsens neuronal loss and contributes to progressive neurological diseases like Parkinson's disease (PD). This inflammatory progression is countered by dynorphin (Dyn), the endogenous ligand of the kappa-opioid receptor (KOR). We show that microglial beta-arrestin mediates the ability of Dyn/KOR to limit endotoxin-elicited production of pro-inflammatory effectors and cytokines, subsequently protecting neurons from inflammation-induced neurotoxicity. Agonist-activated KOR enhances the interaction of beta-arrestin2 with transforming growth factor-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1), disrupting TAK1-TAB1 mediated pro-inflammatory gene expression. We reveal a new physiological role for beta-arrestin in neuroprotection via receptor internalization-triggered blockade of signal effectors of microglial inflammatory neurotoxicity. This result offers novel drug targets in the convergent KOR/beta-arrestin2 and inflammatory pathways for treating microglial inflammatory neuropathologies like PD. |
