Complement C3a Suppresses Spinal Cord Neural Stem Cell Activation by Inhibiting UCHL1 via the NF-κB p65/Nrf2 Pathway.

ABSTRACT: Activation of spinal cord neural stem cells (NSCs) and subsequent neurogenesis holds a promising alternative for spinal cord injury (SCI) repair. Our previous study demonstrated that complement C3a, derived from reactive astrocytes, inhibits NSC proliferation by suppressing protein aggregate clearance through the deubiquitinating enzyme ubiquitin carboxy-terminal hydrolase L1 (UCHL1)-proteasome system post-SCI. However, the potential molecular mechanism by which C3a modulates NSC activation via this pathway remains unclear. Here, we revealed that C3a/C3a receptor (C3aR) signaling activated NF-κB p65, which in turn inhibited Nrf2 activity and UCHL1 expression, resulting in diminished proteasome activity and the accumulation of protein aggregates, and ultimately impaired NSC activation. Both

SUBMITTER: Ding L 

PROVIDER: S-EPMC12789345 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature