P21 (P021)

Also known as: P021

Evidence: Preclinical

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Overview

P021, a CNTF-derived peptide (Ac-DGGL plus an adamantylated glycine, amide) that improved memory and neurogenesis in mouse and rat models of Alzheimer's disease and aging, given in the diet.

P21 (P021) is a neurotrophic peptide derived from CNTF (Ciliary Neurotrophic Factor). Research shows enhancement of neurogenesis and synaptic plasticity. Studies demonstrate cognitive improvement potential, particularly for memory and learning processes.

Benefits

Neurogenesis and BDNF elevation in rodent models; no human data

Dosing reference

Research dose: Vendor/community range 250 to 1000 mcg daily; no published human dose.
Range: 250 to 1000 mcg, 1x daily

All chronic rodent studies gave P021 in the diet (60 nmol per g of feed), not by injection (Kazim 2014; Baazaoui 2017). No human pharmacokinetic, dose or safety data exist. Community protocols are subcutaneous.

Mechanism

Proposed neurotrophic action. P021 was built from CNTF residues 148 to 151 with an adamantylated glycine added (Li et al., 2010). In mice, adamantane-modified CNTF peptides promoted neurogenesis and synaptic plasticity, and chronic oral dosing had disease-modifying effects in a triple transgenic Alzheimer's model (Kazim et al., 2014). It prevented dendritic and synaptic deficits (Baazaoui and Iqbal, 2017) and lowered cerebrospinal fluid tau in aged rats (Khatoon et al., 2015). No receptor target has been identified.

Evidence

Preclinical: animal or in vitro data only

Adamantane-modified CNTF peptides improved learning and memory and promoted neurogenesis and synaptic plasticity in mice (Li et al., 2010)
Chronic oral treatment had disease-modifying effects in triple transgenic Alzheimer's mice (Kazim et al., 2014)
Treatment rescued cognitive aging in aged rats (Bolognin et al., 2014)
Early treatment prevented developmental delay and Alzheimer-like memory deficits in Ts65Dn Down syndrome mice (Kazim et al., 2017)
P021 was tested in cell and mouse models of CDKL5 deficiency disorder by an independent group (Mottolese et al., 2024)
Human-trial status: none. All animal dosing was dietary or oral, with no injectable study, and nearly all work comes from one group (Iqbal laboratory)

References

Side effects

No human safety data; effects unknown beyond animal studies, where rodent work reported no overt toxicity. Human pharmacokinetics, dosing, and long-term neurological effects are entirely uncharacterized.

Storage

Storage: Refrigerate 2-8°C (36-46°F)
Lyophilized: 2+ years at room temp, 3+ years refrigerated
Reconstituted: 28-30 days refrigerated

Pharmacology

Half-life: Not reported in the sources reviewed; no human data
Bioavailability: Orally active in mice when given in the diet (Kazim et al., 2014); not measured in humans or by injection
Molecular weight: 578.7 Da
Sequence: Ac-DGGL-[adamantylglycine]-NH2