| First Author | Rueda-Carrasco J | Year | 2021 |
| Journal | EMBO Rep | Volume | 22 |
| Issue | 11 | Pages | e51696 |
| PubMed ID | 34569685 | Mgi Jnum | J:318680 |
| Mgi Id | MGI:6810720 | Doi | 10.15252/embr.202051696 |
| Citation | Rueda-Carrasco J, et al. (2021) SFRP1 modulates astrocyte-to-microglia crosstalk in acute and chronic neuroinflammation. EMBO Rep 22(11):e51696 |
| abstractText | Neuroinflammation is a common feature of many neurodegenerative diseases. It fosters a dysfunctional neuron-microglia-astrocyte crosstalk that, in turn, maintains microglial cells in a perniciously reactive state that often enhances neuronal damage. The molecular components that mediate this critical communication are not fully explored. Here, we show that secreted frizzled-related protein 1 (SFRP1), a multifunctional regulator of cell-to-cell communication, is part of the cellular crosstalk underlying neuroinflammation. In mouse models of acute and chronic neuroinflammation, SFRP1, largely astrocyte-derived, promotes and sustains microglial activation, and thus a chronic inflammatory state. SFRP1 promotes the upregulation of components of the hypoxia-induced factor-dependent inflammatory pathway and, to a lower extent, of those downstream of the nuclear factor-kappa B. We thus propose that SFRP1 acts as an astrocyte-to-microglia amplifier of neuroinflammation, representing a potential valuable therapeutic target for counteracting the harmful effect of chronic inflammation in several neurodegenerative diseases. |
