| First Author | Zou Y | Year | 2021 |
| Journal | Front Cell Dev Biol | Volume | 9 |
| Pages | 769229 | PubMed ID | 34977020 |
| Mgi Jnum | J:361428 | Mgi Id | MGI:6853051 |
| Doi | 10.3389/fcell.2021.769229 | Citation | Zou Y, et al. (2021) Programmed Cell Death Protein 1 Blockade Reduces Glycogen Synthase Kinase 3beta Activity and Tau Hyperphosphorylation in Alzheimer's Disease Mouse Models. Front Cell Dev Biol 9:769229 |
| abstractText | Alzheimer's disease (AD) is a central nervous system degenerative disease, with no effective treatment to date. Administration of immune checkpoint inhibitors significantly reduces neuronal damage and tau hyperphosphorylation in AD, but the specific mechanism is unclear. Here, we found that programmed cell death-receptor 1 (PD1) and its ligand PDL1 were induced by an intracerebroventricular injection of amyloid-beta; they were significantly upregulated in the brains of APP/PS1, 5xFAD mice and in SH-SY5Y-APP cell line compared with control. The PD1 and PDL1 levels positively correlated with the glycogen synthase kinase 3 beta (GSK3beta) activity in various AD mouse models, and the PDL1-GSK3beta immune complex was found in the brain. The application of PD1-blocking antibody reduced tau hyperphosphorylation and GSK3beta activity and prevented memory impairments. Mechanistically, we identified PD1 as a critical regulator of GSK3beta activity. These results suggest that the immune regulation of the PD1/PDL1 axis is closely involved in AD. |
