A dipeptide mimetic of NGF loop 4, bis(N-succinyl-L-glutamyl-L-lysine) hexamethylenediamide (GK-2), developed at the Zakusov Research Institute of Pharmacology, has the NGF-like ability to activate TrkA receptors, but unlike NGF, GK-2 activates mainly the PI3K/AKT pathway associated with neuroprotection and has no effect on the MAPK cascade associated with hyperalgesia, the main side effect of NGF.
HSV‑IGF‑1 transfection enhanced EA‑induced neuroplasticity, which manifested as partial recovery in locomotor function, remission hyperpathia, growth of DRG‑derived spared fibers, increased expression of phosphorylated (p‑) phosphatidylinositol 3‑kinase (PI3K) and Akt, and increased pPI3K/PI3K and pAkt/Akt expression ratios.
Protein expression levels of p-PI3K/p-Akt/p-mTOR were amplified in the periaqueductal gray of bone cancer rats, and blocking PI3K-mTOR pathways in the periaqueductal gray attenuated hyperalgesia responses.