Dihexa
A synthetic angiotensin IV derivative reported to promote new synapse formation in rodents. No human data of any kind exists.
Cognitive & Neuro
P21
An eleven-amino-acid fragment of ciliary neurotrophic factor, modified for brain penetration. Rodent data in Alzheimer's models is encouraging; there is no human data.
Overview
Ciliary neurotrophic factor supports the survival of neurons and encourages the birth of new ones in the hippocampus, but the whole protein is far too large to reach the brain from the bloodstream. P21 is a short active fragment of it, chemically modified with adamantane to help it cross the blood-brain barrier and resist breakdown. In mouse models of Alzheimer's disease it increased neurogenesis, reduced tau phosphorylation and improved memory performance.
An adamantylated, tetrahydrofuran-modified undecapeptide derived from the biologically active region of CNTF. Reported to enhance hippocampal neurogenesis, upregulate BDNF expression, inhibit GSK-3β-mediated tau hyperphosphorylation and reduce amyloid pathology in 3xTg-AD and Ts65Dn mouse models, with corresponding improvement in behavioural memory endpoints. Administered orally and subcutaneously in rodents with demonstrated CNS exposure. No investigational new drug programme has produced human data.
Research areas
Alzheimer's diseaseNeurogenesisTau pathologyDown syndrome models
Dosing reported in the literature
Every protocol below is reproduced from a published study or approved labelling, with its source named. These are records of what was studied — not recommendations, and not a suggestion that any of them is appropriate for any person.
| Protocol as reported | Source |
|---|---|
| Chronic subcutaneous or oral P21 in 3xTg-AD mice over several months with cognitive and histological endpoints | Kazim et al., Neurobiology of Disease 2014 |
Trial status
Preclinical only. No human trials of any phase.
Reported safety signals
- No human safety data exists.
- Chronic promotion of neurogenesis and neurotrophic signalling has not been evaluated for long-term consequences in humans.
- Marketed material is unregulated and its identity is unverified.
Common questions
Is P21 the same as the p21 protein in cell biology?
No, and the naming collision causes real confusion. The p21 in cell-cycle biology (CDKN1A) is a cyclin-dependent kinase inhibitor involved in senescence. This P21 is an unrelated CNTF-derived peptide.
Primary sources
- 01
Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease
- 02
Neurotrophic factor small-molecule mimetics for neurodegenerative disease
- 03
Ciliary neurotrophic factor: structure, function and therapeutic potential
Medical disclaimer
This page is for informational and research purposes only. Nothing here constitutes medical advice. The compounds discussed are research chemicals. Consult a qualified clinician before starting any protocol.
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