Modulating GRP75 to restore calcium homeostasis: a novel neuroprotective strategy of CRSE6# in Parkinson's disease models - PubMed
3 hours ago
- #Parkinson's disease
- #Calcium homeostasis
- #Neuroprotection
- CRSE6# from Citri Reticulatae Semen shows neuroprotective effects in Parkinson's disease (PD) models.
- The study focuses on restoring calcium homeostasis by modulating GRP75, a key protein in the IP3R-GRP75-VDAC1 axis.
- In vitro, CRSE6# reduced apoptosis, restored mitochondrial membrane potential, and decreased reactive oxygen species in rotenone-induced cells.
- In vivo, CRSE6# improved motor deficits, spatial memory, reduced α-synuclein aggregation, and suppressed neuroinflammation in A53T-αSyn-Tg mice.
- Serum analysis identified 186 absorbed components, with eight high-confidence compounds like kaempferol and hesperidin.
- Mechanistically, CRSE6# suppresses ER stress and disrupts the IP3R-GRP75-VDAC1 complex, alleviating mitochondrial calcium overload.
- RNA sequencing and gene interference confirmed GRP75 as a key target in calcium signaling pathways for CRSE6#'s neuroprotective effects.
- The findings highlight CRSE6# as a potential natural neuroprotective agent for PD by regulating GRP75-mediated calcium signaling.