TAT-QFNP12 is a peptide corresponding to the 302 to 313 amino acid domain of the protein phosphatase PPM1A, made cell permeable by the addition of TAT, and is a key fragment involved in the binding of PPM1A to the cytoplasmic protein NDRG2. TAT-QFNP12 blockade of the binding of NDRG2 with PPM1A allows PPM1A to enter the nucleus and dephosphorylate Smad2/3, preventing transcription and production of matrix metalloproteinase 9 (MMP-9). Unwanted increased levels of MMP-9 have an important part in blood-brain barrier (BBB) injury in subarachnoid haemorrhage (SAH) and can critically exacerbate poor prognosis. In mouse models of SAH, TAT-QFNP12 dose-dependently inhibits MMP-9 expression and Smad2/3 phosphorylation, and significantly reduces brain edema and neurological deficits, demonstrating that TAT-QFNP12 can protect the blood-brain barrier after SAH and alleviate secondary nerve injury.
