P21

P21, also written P021, is a small peptidergic compound with the structure Ac-DGGLAG-NH2. It was derived by epitope mapping from the most active region of ciliary neurotrophic factor (CNTF), yielding a tetrapeptide core. An adamantylated glycine was added at the C-terminus to increase blood-brain barrier permeability and reduce breakdown by exopeptidases. The N-terminal acetyl group and C-terminal amide shown in the structure are further terminal modifications. The literature describes it as a neurotrophic peptide mimetic.

P21 in the research literature

Studies of P021 have mostly tracked neurotrophic and synaptic markers in rodents. In aged rats, researchers reported increased BDNF expression and higher neurogenesis and synaptic marker levels than in aged vehicle controls. Hippocampal myo-inositol concentration, measured by magnetic resonance spectroscopy, was lower. In triple-transgenic mouse lines, exposure early in development was associated with higher phosphorylated CREB and BDNF, with activation of PLC/PKC, MEK/ERK and PI3K/Akt signaling cascades. PSD-95 levels and CREB activity were also studied in these lines.

In SH-CDKL5-KO cells, a neuronal cell line lacking CDKL5, P021 was reported to shift neuronal proliferation, survival and maturation measures and GSK3β signaling toward those of control cells. In the same study, longer in vivo exposure in Cdkl5 knockout mice did not raise brain BDNF levels.