Sonic Hedgehog-Gli1 signaling promotes microglial activation via the IKKβ/NF-κB pathway - PubMed
7 hours ago
- #Microglial Activation
- #Parkinson's Disease
- #Neuroinflammation
- Sonic Hedgehog (Shh)-Gli1 signaling is crucial for neuronal development and cell proliferation.
- Shh is expressed in neurons and astrocytes, and upregulated in Parkinson's disease (PD) mouse models.
- Microglia express Shh receptor PTCH1 and downstream effectors SMO and Gli1 but do not produce Shh.
- Exogenous Shh or SMO agonist SAG induces microglial activation and amplifies LPS-driven inflammation via Shh-Gli1-IKKβ pathway.
- Inhibition of Shh-Gli1 signaling suppresses microglial activation by attenuating NF-κB signaling.
- SMO inhibitor GDC-0449 alleviates neuroinflammation and protects dopaminergic neurons in LPS-challenged mice.
- Microglia-specific Ptch1 knockout increases susceptibility to LPS-induced neuroinflammation and dopaminergic neuronal loss.
- Shh-Gli1 signaling plays a pivotal role in microglia-driven neuroinflammation and dopaminergic neuronal injuries.