A Novel Mechanism by which harpagide protects against cerebral ischemia:Focus on Grp75 and MAMs Calcium Homeostasis - PubMed
4 days ago
- #Calcium homeostasis
- #Ischemic stroke
- #Neuroprotection
- Harpagide, derived from Radix Scrophulariae, shows anti-ischemic effects by regulating calcium homeostasis at MAMs (endoplasmic reticulum-mitochondria contact sites).
- The study explores harpagide's neuroprotective role via the IP3R1-Grp75-VDAC1 axis, impacting calcium transfer and ER-mitochondria contact in a time-dependent manner.
- In vivo (MCAO mice) and in vitro (OGD PC12 cells) models demonstrated harpagide's ability to reduce infarct volume, neurological deficits, and mitochondria-mediated apoptosis.
- Harpagide transiently enhances IP3R1-Grp75 binding at 4h post-OGD but downregulates Grp75 by 6h, reducing calcium overload and ER-mitochondria contact.
- Grp75 knockdown inhibited harpagide's protective effects, while Grp75 overexpression reinforced them, confirming Grp75 as a key target.
- The study highlights harpagide's phase-dependent modulation of Grp75, offering a novel therapeutic mechanism for ischemic stroke.