Well-defined peptide-conjugated intracellular-acidity-sensitive nanoassemblies for tumor-targeted anticancer drug delivery
JOURNAL OF CONTROLLED RELEASE(2017)
Abstract
Neuronal cell death following traumatic brain injury (TBI) is a considerable contributor to neurological deficits. In our work, we explored the functions of Mammalian STE20-like kinase-1 (Mst1), a apoptosis-promoting kinase and also a pivotal bridgebuilder of apoptotic signaling, in the etiopathogenesis of an experimental rat model of TBI. We found that the phosphorylation level of Mst1 in injured area was significantly increased after TBI. Furthermore, we discovered that inhibition of Mst1 phosphorylation can effectively reduce neuronal cell death by inhibiting the activation of caspase 3 and suppressing the damage of DNA during TBI. In addition, the decreased of Mst1 phosphorylation level, not only reduced brain edema and blood-brain barrier (BBB) damage in injured region but also weakened the impairment of neurologic behavior during TBI. In conclusion, our work demonstrates that Mst1 plays an important role in TBI-induced neuronal cell death, suggesting that Mst1 is expected to be a potential therapeutic target for TBI.
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Key words
drug delivery system,polypeptide,cell-penetrating peptides,schiff's base
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