Neurotrophic Research
Research Only
P21 (With Adamantane)
Also known as: P021, Peptide 021, P21 peptide
Synthetic CNTF-based peptide with an added adamantyl-glycine (P021). Studied in rodent research on hippocampal neurogenesis.
Research overview
P021 (also written P21) is a small synthetic peptide designed by Khalid Iqbal's group at the New York State Institute for Basic Research. It is built on a four-amino-acid region (Asp-Gly-Gly-Leu) of ciliary neurotrophic factor (CNTF), a growth factor for nerve cells, with an adamantyl-glycine (glycine carrying a bulky ring-shaped adamantane group) added to help it cross into the brain. The published P021 work uses this adamantane-modified form. In normal adult mice, treated animals had more new nerve cells in the hippocampus and better learning and memory test scores (Li et al., FEBS Lett 2010). The same group later reported smaller age-related memory declines in aged rats and less abnormal tau protein in a mouse model of Alzheimer's disease.
Nearly all studies involve the developing group, whose lead scientist holds patents on P021. A 2024 study in a mouse model of CDKL5 deficiency saw effects in cultured cells but only limited change in the mice (Mottolese et al., 2024). There are no published human studies, and human safety and pharmacokinetics are unknown. Supplied for laboratory research use only.
Mechanism of action
In cell and rodent studies by its developers, P021 blocks signalling by leukaemia inhibitory factor (LIF) and raises levels of brain-derived neurotrophic factor (BDNF). BDNF then acts through its receptor, TrkB, and the PI3K-AKT pathway to lower the activity of GSK-3 beta, an enzyme that adds phosphate groups to tau protein. Its effect on TrkB is therefore described as indirect, through BDNF, rather than by binding TrkB itself.