Mechanistic insights into cannabidiol-mediated TrkB activation via FRS2 interaction in attenuating Alzheimer's disease pathology and cognitive impairment - PubMed
5 hours ago
- #Alzheimer's disease
- #Cannabidiol
- #TrkB signaling
- CBD ameliorates cognitive and emotional deficits in 3×Tg-AD mice by restoring synaptic integrity and plasticity.
- CBD activates TrkB signaling independently of BDNF, suppressing tau hyperphosphorylation via the PI3K/AKT/GSK3β pathway.
- CBD attenuates neuroinflammation and amyloid pathology by inhibiting the JAK2/STAT3/SOCS1 axis.
- FRS2, a core adaptor protein of TrkB, is identified as a direct molecular target of CBD.
- Molecular dynamics simulations show CBD stabilizes the FRS2-TrkB interface, facilitating TrkB activation.
- Genetic knockdown of FRS2 abolishes CBD-induced TrkB signaling and neuroprotective effects in AD models.