P21 | PeptideDB

Overview

P21 is a synthetic tetrapeptide derived from an active region of Ciliary Neurotrophic Factor (CNTF). Developed to capture the neurotrophic benefits of CNTF without its appetite-suppressant side effects, P21 has shown promise in preclinical studies for enhancing neurogenesis and cognitive function.

The peptide represents a targeted approach to promoting brain health through neurotrophic factor modulation.

Sequence: Ac-DGGL-NH2 (Acetyl-Asp-Gly-Gly-Leu-amide)

Mechanism of Action

P21's mechanisms center on neurotrophic signaling:

BDNF Enhancement

Increases Brain-Derived Neurotrophic Factor expression
Elevates BDNF levels in hippocampus
Promotes downstream TrkB signaling
Sustained effects on neuroplasticity

Neurogenesis Promotion

Stimulates neural stem cell proliferation
Increases dentate gyrus neurogenesis
Promotes neuronal differentiation
Enhances survival of new neurons

CNTF Pathway

Derived from CNTF active region
Mimics CNTF neurotrophic effects
Avoids CNTF's appetite suppression
Selective neurological activity

Synaptic Enhancement

Increases synaptic density
Improves dendritic complexity
Enhances long-term potentiation
Supports memory consolidation

Research Summary

Neurogenesis Studies

Hippocampal Neurogenesis (Mouse)

Significantly increased BrdU+ cells (new neurons)
Enhanced survival of newborn neurons
Improved integration into circuits
Effects observed with chronic treatment

Aging Models

Restored neurogenesis in aged mice
Improved cognitive function in aged animals
Reversed age-related BDNF decline

Cognitive Enhancement

Model	Finding
Morris water maze	Improved spatial memory
Novel object recognition	Enhanced recognition memory
Aged animals	Reversed cognitive decline
Alzheimer's models	Reduced deficits

Alzheimer's Disease Models

3xTg-AD Mice

Reduced tau pathology
Decreased amyloid burden
Improved cognitive performance
Restored synaptic markers

Neuroprotective Effects

Protected against neurodegeneration
Reduced neuroinflammation
Preserved synaptic function
Maintained neuronal survival

Key Limitations

No human clinical trials
All data from rodent models
Long-term safety unknown
Optimal human dosing not established
Translation to humans uncertain

Pharmacokinetics

Parameter	Estimated Value
Half-life	Unknown in humans
Bioavailability	Demonstrated in animal models
CNS penetration	Yes (crosses BBB)
Active doses	mg/kg range in animal studies

Note: Human pharmacokinetic data not available

Common Protocols

Note: P21 is a research compound with no human clinical trials. The following represents research community protocols.

Research Community Protocols

Typical Dosing Ranges:

Intranasal: 1-2 mg daily
Subcutaneous: 500 mcg - 2 mg daily
Duration: 4-8 week cycles typical

Administration Routes:

Intranasal (most common in research community)
Subcutaneous injection
Oral (bioavailability uncertain)

Reconstitution

Typically supplied as lyophilized powder
Reconstitute with bacteriostatic water
Store at 2-8°C after reconstitution
Use within 4-6 weeks

Timing

Once or twice daily dosing
Some prefer morning administration
Chronic administration used in studies

Side Effects

Reported (Limited Data)

Given minimal human use data:

Nasal irritation (intranasal)
Headache
Fatigue
Mild mood changes

Theoretical Concerns

Long-term effects of enhanced neurogenesis unknown
Effect on existing neural circuits uncertain
Cancer considerations (growth promotion)
Developmental concerns (not for those under 25)

Safety Notes

Novel research compound
Limited human safety data
Long-term effects unstudied
Caution warranted

Interactions

Theoretical Interactions

Other neurotrophic compounds (unknown)
Antidepressants (BDNF modulation)
Growth factors
Other nootropics

Contraindications (Theoretical)

Active cancer
Pregnancy/nursing
Age under 25
Neurological conditions (consult specialist)

Community Insights

Aggregated from limited research community reports. Should be viewed with caution.

Commonly Reported Experiences

Subtle cognitive improvements
Enhanced memory over time
Improved learning
Mood stabilization
Effects develop gradually
Less acute than other nootropics

Practical Tips

Effects may take weeks to manifest (neurogenesis timeline)
Consistent dosing important
Quality sourcing critical
Often used in longer cycles

Common Stacks

P21 + Semax (neurotrophic combination)
P21 + NSI-189 (neurogenesis focus)
P21 in comprehensive nootropic protocols

Expectations

Not an acute cognitive enhancer
Effects build over time
Aimed at long-term brain health
Subtle rather than dramatic

References

Bolognin S, et al. An experimental rat model of sporadic Alzheimer's disease and rescue of cognitive impairment with a neurotrophic peptide. Acta Neuropathol. 2012;123(6):785-99.
Li B, et al. Rescue of cognitive function in a mouse model of Alzheimer's disease by a neurotrophic peptide. Curr Alzheimer Res. 2012;9(7):777-85.
Chohan MO, et al. Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and memory by a neurotrophic peptide. Neurobiol Aging. 2011;32(8):1420-34.
Kazim SF, et al. Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease. Neurobiol Dis. 2014;71:110-30.
Blanchard J, et al. A run of Alzheimer's disease-relevant cognitive deficits in a mouse model is rescued by a neurogenic peptide. Neurobiol Aging. 2010;31(11):1939-52.