P21
P021 | CNTF-Derived Neurogenic Peptide
P21 is a nootropic peptide derived from ciliary neurotrophic factor (CNTF) that enhances neurogenesis and cognitive function. It contains an adamantane moiety that enables blood-brain barrier penetration. Research shows it increases BDNF expression, inhibits LIF signaling to promote neurogenesis, and reduces tau and amyloid pathology in Alzheimer's disease models. Remarkably, P21 can boost neurogenesis in diseased brains above levels seen in healthy untreated brains.
Mechanism of Action
P21 operates through multiple pathways: it inhibits leukemia inhibitory factor (LIF) signaling, removing a key roadblock to neurogenesis and shifting the brain toward a more embryologic state favoring neuron growth. It increases brain-derived neurotrophic factor (BDNF) expression and activates the BDNF/TrkB/PI3-K/AKT/GSK3β pathway. This pathway modulation improves cognitive function and reduces tau and amyloid pathologies.
Key Benefits
- Potent promotion of neurogenesis in the dentate gyrus
- Increased BDNF expression
- Reduced tau protein pathology
- Reduced amyloid-beta plaque formation
- Improved cognitive function and memory
- Restored synaptic deficits in cortex and hippocampus
- Reduced mortality rate in AD models
- Crosses blood-brain barrier effectively
Neurodegenerative Disease
- Alzheimer's Disease
P021 markedly reduced tau pathology, attenuated Aβ generation, and rescued episodic memory impairment in 3xTg-AD mice.
- Neurodegeneration Prevention
Treatment during synaptic compensation period can prevent neurodegeneration and reduce mortality.
- Tau Pathology
Robust attenuation of tau pathologies through BDNF/TrkB/PI3-K/AKT/GSK3β pathway.
Cognitive Enhancement
- Neurogenesis
Enhances dentate gyrus neurogenesis so effectively it exceeds levels in healthy untreated brains.
- Memory Processes
Enhances memory processes through increased BDNF and restored synaptic function.
- Age-Related Cognitive Decline
May reduce natural decline in learning and memory in aged models by rescuing neurogenesis deficit.
Neuroprotection
- Synaptic Plasticity
Restores synaptic deficits in cortex and hippocampus.
- Neuronal Plasticity
Rescues deficits in neuronal plasticity.
P21 has not yet been tested in human clinical trials. Research protocols in animal models use subcutaneous or intraperitoneal injection. The adamantane moiety enables blood-brain barrier penetration for CNS effects.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Research protocol | Variable by study | Daily | SubQ or IP |
Reconstitution Instructions
- Bacteriostatic water (BAC)
- Insulin syringes
- Alcohol swabs
- Peptide vial
- Sterile work surface
- 1 Clean work area and hands thoroughly
- 2 Calculate required BAC water volume
- 3 Draw BAC water into syringe
- 4 Inject slowly down vial side
- 5 Gently swirl until dissolved (never shake)
- 6 Store in refrigerator
Different nootropic mechanisms; may complement each other.
Both promote neurogenesis through different pathways.
No known negative interactions; different mechanisms.
Different cognitive enhancement mechanisms.
BDNF elevation begins
Neurogenesis enhancement measurable
Cognitive improvements in research models
Disease-modifying effects in AD models
Common Side Effects
- Limited data - primarily preclinical research
- Generally well-tolerated in animal studies
Stop Signs - Discontinue if:
- Allergic reactions
- Unusual neurological symptoms
Contraindications
- Not approved for human use
- Pregnancy or breastfeeding
- Unknown safety profile in humans
Good Signs
- White lyophilized powder
- Clear solution after reconstitution
- High purity (>95%)
- Intact vacuum seal
Warning Signs
- Research chemical - limited quality standards
Bad Signs
- Discoloration
- Cloudy solution
- Particulates visible
- P021 Treatment in 3xTg-AD MiceJournal of Alzheimer's Disease (2018)
P021 markedly reduced tau pathology, attenuated Aβ, rescued episodic memory, and reduced mortality in AD mice.
- P21 and BDNF/TrkB PathwayNeuropharmacology (2019)
Disease-modifying effect via BDNF/TrkB/PI3-K/AKT/GSK3β pathway; rescued neurogenesis and cognition.
- P21 in Cognitive AgingNeurobiology of Aging (2017)
May reduce age-related cognitive decline by restoring BDNF expression and synaptic function.
- P21 as Promising AD Drug CandidateAlzheimer's Research & Therapy (2020)
Beneficial effects in preclinical studies make P21 highly promising for AD drug development.
Disclaimer
This information is for educational and research purposes only. Consult a healthcare professional before use.