P21
Cognitive Enhancement / Nootropic PeptideresearchAlso known as: P021, CNTF-derived peptide
A small synthetic peptide derived from ciliary neurotrophic factor (CNTF) that promotes neurogenesis and enhances cognitive function by inhibiting leukemia inhibitory factor (LIF) signaling.
Overview
P21 is a synthetic tetrapeptide developed by Dr. Khalid Iqbal at the New York State Institute for Basic Research in Developmental Disabilities. It is derived from the active region of ciliary neurotrophic factor (CNTF) but modified to be more stable and brain-penetrant. P21 promotes neurogenesis in the hippocampal dentate gyrus and reduces levels of hyperphosphorylated tau, making it a candidate for Alzheimer's disease and cognitive decline research. Unlike full-length CNTF, P21 lacks the LIF-activating domain, which means it promotes neurogenesis without the appetite-suppressing and weight-loss side effects of CNTF. In animal models, P21 has been shown to rescue cognitive deficits, increase dendritic spine density, and reduce neurodegeneration markers.
Mechanism of Action
P21 acts through several neuroplasticity-related pathways: (1) Mimics the neurotrophic activity of CNTF by activating similar downstream signaling; (2) Increases BDNF expression in the hippocampus, promoting neuronal survival and synaptic plasticity; (3) Promotes neurogenesis in the dentate gyrus of the hippocampus; (4) Reduces hyperphosphorylated tau protein levels, a hallmark of Alzheimer's pathology; (5) Inhibits LIF signaling selectively, avoiding the cachectic effects of full-length CNTF; (6) Enhances dendritic complexity and spine density in hippocampal neurons.
Molecular Formula
C25H40N6O6
Molecular Weight
520.62 g/mol
Sequence
Ac-DGGL-OH (Ac-Asp-Gly-Gly-Leu-OH)
Dosage Protocols
Dose Range
500mcg – 1000mcg
Frequency
Once daily
Route
intranasal
Cycle Length
4-12 weeks
Intranasal is the preferred route for direct CNS delivery. Reconstitute in bacteriostatic water. Experimental dosing based on animal study extrapolation.
Source: Community protocols derived from preclinical research
Side Effects
| Effect | Severity |
|---|---|
| Nasal irritation | mild |
| Headache | mild |
| Mild fatigue | mild |
| Vivid dreams | mild |
Pros & Cons
Promotes actual neurogenesis (new neuron growth) in the hippocampus, not just neurotransmitter modulation
Reduces hyperphosphorylated tau — directly relevant to Alzheimer's disease pathology
Derived from CNTF but engineered to avoid appetite suppression and cachexia side effects
Small molecule size allows blood-brain barrier penetration and multiple administration routes
Very limited research — only a handful of animal studies from one research group
No human clinical trials or established safety data
Dosing protocols are entirely anecdotal and extrapolated from animal models
Limited availability and few reliable peptide suppliers carry it
Research Studies
Legal Status
Not FDA-approved. Available as a research chemical. No regulatory restrictions in most jurisdictions.
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