| Expression pattern: |
UP |
| Associated gene: |
PDE4B, Smurf2, Sfpq, Hnrnpa1, Pura, Hnrnpg |
| Associated microRNA: |
- |
| Biological function: |
Promotes microglial pro-inflammatory activation, limits amyloid-beta uptake, and contributes to neuroinflammation and cognitive decline in AD; knockdown enhances microglial protective response to Abeta and alleviates AD pathologies. |
| Molecular mechanism: |
circDlg1 forms a ternary complex with PDE4B and the E3 ligase Smurf2, blocks Smurf2-mediated ubiquitination-dependent degradation of PDE4B, lowers cAMP and suppresses PKA/CREB anti-inflammatory signaling. |
| Biological pathway or process: |
NF-kappaB (other); inflammation (promotes); immune regulation (promotes); other pathway/process (promotes) |
| Detected method: |
Q
H
M
|
| Validation methods: |
Microarray; RT-qPCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RNase R Treatment; Actinomycin D / DRB Stability Assay; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Western Blot; ELISA; Transfection; Flow Cytometry（Non-apoptosis/cycle）; IF (Immunofluorescence); In Vivo Animal Model; Bioinformatics Analysis |
| Clinical significance: |
Microglia of AD patients expressed more circDLG1 than those of healthy controls. |
| Description: |
circDlg1 is up-regulated in AD microglia (APP/PS1 mice and human AD cortex). It binds PDE4B and Smurf2 to protect PDE4B from ubiquitination-dependent degradation, lowering cAMP and suppressing PKA/CREB anti-inflammatory signaling, thereby promoting neuroinflammation. Microglia-specific circDlg1 knockdown enhances Abeta engagement/uptake, reduces neuroinflammation and Abeta burden, and improves cognition in APP/PS1 mice. |
| Confidence score: |
0.7958 |