| First Author | Fan Q | Year | 2019 |
| Journal | J Exp Med | Volume | 216 |
| Issue | 8 | Pages | 1891-1903 |
| PubMed ID | 31209068 | Mgi Jnum | J:280272 |
| Mgi Id | MGI:6364568 | Doi | 10.1084/jem.20182238 |
| Citation | Fan Q, et al. (2019) The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer's amyloid pathology. J Exp Med 216(8):1891-1903 |
| abstractText | The membrane-anchored CX3CL1 is best known to exert its signaling function through binding its receptor CX3CR1. This study demonstrates a novel function that CX3CL1 exerts. CX3CL1 is sequentially cleaved by alpha-, beta-, and gamma-secretase, and the released CX3CL1 intracellular domain (CX3CL1-ICD) would translocate into the cell nucleus to alter gene expression due to this back-signaling function. Amyloid deposition and neuronal loss were significantly reduced when membrane-anchored CX3CL1 C-terminal fragment (CX3CL1-ct) was overexpressed in Alzheimer's 5xFAD mouse model. The reversal of neuronal loss in 5xFAD can be attributed to increased neurogenesis by CX3CL1-ICD, as revealed by morphological and unbiased RNA-sequencing analyses. Mechanistically, this CX3CL1 back-signal likely enhances developmental and adult neurogenesis through the TGFbeta2/3-Smad2/3 pathway and other genes important for neurogenesis. Induction of CX3CL1 back-signaling may not only be a promising novel mechanism to replenish neuronal loss but also for reducing amyloid deposition for Alzheimer's treatment. |
