Shh-S100A10 axis curbs neuronal PANoptosis after ischemic stroke

Area of Science:

• Neuroscience
• Cell Biology
• Pathophysiology

Background:

• Acute ischemic stroke causes significant disability and neuronal death.
• PANoptosis, a cell death pattern involving pyroptosis, apoptosis, and necroptosis, is implicated in ischemic brain injury.
• The precise mechanisms of PANoptosis in stroke remain unclear.

Purpose of the Study:

• To elucidate the role of S100 calcium-binding protein A10 in neuronal PANoptosis following ischemic brain damage.
• To investigate the effects and mechanisms of sonic hedgehog and S100 calcium-binding protein A10 on PANoptosis.

Main Methods:

• Utilized cellular and animal models of ischemic stroke.
• Examined the expression of S100 calcium-binding protein A10.
• Investigated the impact of S100 calcium-binding protein A10 knockdown on PANoptosis.
• Assessed the effects of sonic hedgehog treatment.

Main Results:

• S100 calcium-binding protein A10 was upregulated in ischemic stroke models.
• Knockdown of S100 calcium-binding protein A10 worsened PANoptosis and related protein levels.
• Sonic hedgehog treatment increased S100 calcium-binding protein A10 and reduced PANoptosis.

Conclusions:

• Sonic hedgehog intervention effectively mitigated neuronal PANoptosis in ischemic stroke.
• S100 calcium-binding protein A10 plays a role in regulating PANoptosis after cerebral ischemia.
• The combination of S100 calcium-binding protein A10 and sonic hedgehog offers potential therapeutic strategies for ischemic stroke.