| First Author | Feng B | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 34 | PubMed ID | 34407949 |
| Mgi Jnum | J:310416 | Mgi Id | MGI:6762313 |
| Doi | 10.1126/sciadv.abh2307 | Citation | Feng B, et al. (2021) Planar cell polarity signaling components are a direct target of beta-amyloid-associated degeneration of glutamatergic synapses. Sci Adv 7(34) |
| abstractText | The signaling pathway directly controlling the maintenance of adult glutamatergic synapses has not been well understood. Planar cell polarity (PCP) signaling components were recently shown to play essential roles in the formation of glutamatergic synapses. Here, we show that they are localized in the adult synapses and are essential for their maintenance. Synapse loss at early stages of Alzheimer's disease is thought to be induced by beta-amyloid (Abeta) pathology. We found that oligomeric Abeta binds to Celsr3 and assists Vangl2 in disassembling synapses. Moreover, a Wnt receptor and regulator of PCP signaling, Ryk, is also required for Abeta-induced synapse loss. In the 5XFAD mouse model of Alzheimer's disease, Ryk conditional knockout or a function-blocking monoclonal Ryk antibody protected synapses and preserved cognitive function. We propose that tipping of the fine balance of Wnt/PCP signaling components in glutamatergic synapses may cause synapse degeneration in neurodegenerative disorders with Abeta pathology. |
