| First Author | Ouyang P | Year | 2024 |
| Journal | Redox Biol | Volume | 70 |
| Pages | 103064 | PubMed ID | 38320455 |
| Mgi Jnum | J:349300 | Mgi Id | MGI:7581528 |
| Doi | 10.1016/j.redox.2024.103064 | Citation | Ouyang P, et al. (2024) SELENOK-dependent CD36 palmitoylation regulates microglial functions and Abeta phagocytosis. Redox Biol 70:103064 |
| abstractText | Amyloid-beta (Abeta) is a key factor in the onset and progression of Alzheimer's disease (AD). Selenium (Se) compounds show promise in AD treatment. Here, we revealed that selenoprotein K (SELENOK), a selenoprotein involved in immune regulation and potentially related to AD pathology, plays a critical role in microglial immune response, migration, and phagocytosis. In vivo and in vitro studies corroborated that SELENOK deficiency inhibits microglial Abeta phagocytosis, exacerbating cognitive deficits in 5xFAD mice, which are reversed by SELENOK overexpression. Mechanistically, SELENOK is involved in CD36 palmitoylation through DHHC6, regulating CD36 localization to microglial plasma membranes and thus impacting Abeta phagocytosis. CD36 palmitoylation was reduced in the brains of patients and mice with AD. Se supplementation promoted SELENOK expression and CD36 palmitoylation, enhancing microglial Abeta phagocytosis and mitigating AD progression. We have identified the regulatory mechanisms from Se-dependent selenoproteins to Abeta pathology, providing novel insights into potential therapeutic strategies involving Se and selenoproteins. |
