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Free U.S. shipping on orders over $150P21 is a synthetic peptide designed as a mimetic of ciliary neurotrophic factor (CNTF), a neurotrophin involved in neuronal survival, synaptic maintenance, and central repair pathways.
While native CNTF is a large protein with limited permeability and complex receptor interactions, P21 distills CNTF’s key functional domains into a short, bioactive sequence engineered for stability and targeted signaling [1].
One of the biggest advantages of P21 is its ability to cross the blood–brain barrier (BBB). Its small molecular size allows it to access central nervous system tissues more efficiently than full-length neurotrophic proteins [2].
This distinguishes P21 from broader neurotrophic blends such as cerebrolysin, which rely on multi-peptide mixtures and indirect peripheral effects [3].
Cerebrolysin contains fragments derived from porcine brain proteins and act through diffuse signaling. P21, in contrast, is a receptor-specific mimetic designed to emulate a single neurotrophin’s core actions.
P21’s ability to activate CNTF-related neurotrophic pathways can help support neuronal growth, differentiation, and long-term structural adaptability.
A core feature of P21’s activity is promoting neurogenesis, especially within brain regions where adult neural stem cells remain active [4].
P21 also interacts with pathways involved in synaptic plasticity, the process by which neurons strengthen, weaken, or remodel their connections in response to new information [2].
Because P21 is small enough to cross the blood–brain barrier, these effects occur in a more targeted and timely fashion.
P21 has attracted scientific interest for its potential relevance to pathways implicated in Alzheimer’s disease.
P21’s interaction with STAT3 and other CNTF-responsive intracellular cascades may help reinforce processes that protect neurons from [5]:
all hallmarks frequently in Alzheimer’s models.
Another area of interest is P21’s potential influence on amyloid- and tau-associated stress responses.
An in vivo study in a 3xTg-AD transgenic mouse model of Alzheimer’s disease evaluated effects of 12 months of chronic oral P21.
Female 3xTg-AD mice and wild-type controls were given P21 in their diet for 12 months, starting at 9-10 months of age when AD symptoms developed [6]. P21 diets resulted in:
These findings support P21 as a promising neurotrophic peptide mimetic with therapeutic potential to shift Alzheimer’s disease pathology from neurodegeneration toward regeneration.
P21 has also generated interest in research exploring neurodevelopmental pathways, because CNTF signaling plays a role in neuronal differentiation, axonal guidance, and early circuit formation [7].
During development, CNTF influences how neural progenitors mature into functional neurons and how connections between brain regions are refined.
A combined in vitro/in vivo study evaluated the therapeutic potential of P21 in a mouse model of CDKL5 deficiency disorder (CDD) [8].
CDD is an X-linked disorder that results in seizures, developmental and intellectual delays, and usually requires lifelong care. P21 administration resulted in:
There were limited effects in vivo, as P21 resulted in minimal behavioral improvement. This could be due to differences in bioavailability, timing, or developmental windows between in vitro and in vivo systems.
P21 is not just limited to rare neurodevelopmental disorders.
Prenatal to early postnatal treatment with the CNTF-derived peptide mimetic P021 was tested in Ts65Dn mice, a Down syndrome model that also develops Alzheimer’s-like memory deficits [9].
Early P021 intervention rescued developmental delays in pups and restored hippocampus-dependent memory in adulthood. The treatment:
These results demonstrate that enhancing neurotrophic support during critical periods of early brain development can prevent lifelong cognitive impairment and Alzheimer’s-like pathology associated with trisomy 21.
Research Use Only. All findings described above are derived from preclinical studies (animal models and in vitro experiments). P21 is not approved by the FDA for any diagnostic or therapeutic use in humans. Genesis Peptides makes no claims regarding human clinical efficacy. This product is sold exclusively for laboratory research.
Every lot undergoes six independent assays before release. Results are published in the lot-specific Certificate of Analysis.
P021 (also written P21) is a neurotrophic and neurogenic tetra-peptide derived from the most active region of the ciliary neurotrophic factor (CNTF) by epitope mapping. In a review, the authors describe P021 as a small neurotrophic and neurogenic peptide mimetic compound discovered in their laboratory, which was found to overcome difficulties in administering whole neurotrophic factor proteins. In a study in rats, chronic oral administration of P021, a small peptidergic neurotrophic compound derived from CNTF, significantly reduced the age-dependent decline in learning and memory in 22 to 24-month-old Fisher rats.
P21 is also listed as P021 and is a ciliary neurotrophic factor (CNTF) derived peptidergic compound with the sequence Ac-DGGLAG-NH2. In a study in 3xTg-AD transgenic mice and wild-type control mice, P021 (Ac-DGGLAG-NH2) was given orally during prenatal to early postnatal development. A separate report on chronic oral treatment in a transgenic mouse model of AD gives the sequence as Ac-DGGL(A)G-NH2, with the A written in parentheses.
The adamantylated glycine was added to the C-terminal of P21 (also called P021) to increase its blood-brain barrier permeability. The same modification was also intended to decrease degradation of the peptide by exopeptidases, with the stated aim of making it druggable.
According to a review, P21 (also listed as P021) is a neurogenic and neurotrophic compound that enhances dentate gyrus neurogenesis and memory processes. The review describes this action as occurring by inhibiting leukemia inhibitory factor (LIF) signaling and increasing brain-derived neurotrophic factor (BDNF) expression. In 3xTg-AD mice, the disease-modifying effect of P21 was probably mediated via increased BDNF expression, which led to decreased glycogen synthase kinase-3-β (GSK3β) activity.
In 3xTg-AD mice treated with P021, the authors found increased brain-derived neurotrophic factor (BDNF) expression and decreased glycogen synthase kinase-3β (GSK3β) activity, and they suggested this probably mediated the compound's disease-modifying effect. A review article describes P021 as robustly inhibiting abnormal tau hyperphosphorylation through a BDNF-mediated decrease in GSK-3β activity, which is a major tau kinase.
In 3xTg-AD mice, P21 (also called P021) rescued dendritic and synaptic deficits, boosted neurogenesis, and reversed cognitive impairment. P21 treatment rescued cognitive deficits at 4 months of age, reduced abnormal hyperphosphorylation and accumulation of tau at known major Alzheimer's neurofibrillary pathology-associated sites, and decreased amyloid-beta plaque load at 22 months in 3xTg-AD mice. P21 treatment also rescued deficits in cognition, neurogenesis, and synaptic plasticity in 3xTg-AD mice. When given from birth during early development, P21 prevented cognitive impairment, increased expression of pCREB and BDNF, and ameliorated synaptic protein deficit in 4-month-old 3xTg-AD mice.
In 3 × Tg-AD mice, P021 treatment rescued dendritic and synaptic deficits, boosted neurogenesis, and reversed cognitive impairment. In the same animal studies, P021 restored synaptic deficits both in the cortex and the hippocampus. In 3xTg mice, prenatal to early postnatal P021 treatment also ameliorated markers of postsynaptic deficits, including PSD-95 levels and CREB activity.
The authors describe P021, a neurotrophic peptide mimetic, as a potential early prevention strategy for Alzheimer's disease, suggesting that impaired neurotrophic support during early development may be one contributing factor. In animal studies, treatment with P021 during early development was proposed as an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial Alzheimer's disease and related tauopathies. In animals, P021 was presented as a promising neurotrophic compound for preventing synaptic deficit and cognitive impairment when neurotrophic support is given during the period of synaptic compensation. The authors also propose P021 as a promising compound for stimulating endogenous neuroprotective mechanisms as a therapeutic approach to cognitive aging, Alzheimer's disease, and associated neurodegenerative disorders.
In aged rats, P021 significantly reduced myoinositol (INS) concentration in the hippocampus, which was higher in aged than in young rats, as measured by in vivo magnetic resonance spectroscopy. In the same aged rats, treatment with P021 inhibited the deficit in neurogenesis and increased the expression of brain derived neurotrophic factor.
P21 (P021) is described in a review as a small molecular weight, blood-brain barrier permeable compound with suitable pharmacokinetics for oral administration. An adamantylated glycine was added to the C-terminal of P021 to increase its blood-brain barrier permeability and decrease its degradation by exopeptidases. Whole neurotrophic factor proteins were limited by blood-brain barrier impermeability, short half-life and severe side effects, and P021 was reported to overcome these difficulties.
FOR RESEARCH USE ONLY — Products are sold exclusively for in vitro and preclinical laboratory research. Not for human consumption or administration. Not intended for diagnostic or therapeutic use. These statements have not been evaluated by the FDA.