P-21 5mg

Introduction to P-21

P-21 (also known as P021 or Peptide 021) is a synthetic tetrapeptide derived from ciliary neurotrophic factor (CNTF), a naturally occurring protein that promotes neuron growth and survival. Developed through epitope mapping of CNTF’s active region (amino acid residues 148–151), P-21 incorporates an adamantane group at the C-terminus to enhance blood-brain barrier (BBB) permeability and stability against exopeptidase degradation. This modification makes P-21 a promising nootropic peptide for research into cognitive enhancement, neuroprotection, and neurodegenerative disease treatment.

P-21 is primarily studied for its ability to promote neurogenesis, enhance synaptic plasticity, and reduce pathological hallmarks of Alzheimer’s disease (AD), such as amyloid-beta (Aβ) plaques and tau protein accumulation. Preclinical studies in murine models, including the 3xTg-AD mouse model, suggest that P-21 enhances learning, memory, and neuronal repair while reducing neuroinflammation. It is not approved by regulatory bodies like the FDA or EMA for human use and is restricted to in vitro and animal research due to the lack of human clinical trials. Its potential applications include Alzheimer’s, Parkinson’s, and other cognitive disorders, though further research is needed to establish safety and efficacy.

How P-21 Works

P-21 mimics the neurotrophic effects of CNTF by activating the CNTF receptor complex (CNTFRα, gp130, LIFRβ), which triggers downstream signaling pathways, including JAK/STAT, PI3K-Akt, and MAPK/ERK. These pathways promote neuronal survival, differentiation, and synaptic plasticity. Unlike native CNTF, which has poor BBB permeability and induces antibody formation when administered systemically, P-21’s adamantane modification enhances CNS penetration and stability, allowing it to act without eliciting an immune response.

P-21 increases brain-derived neurotrophic factor (BDNF) expression, which supports neuron growth, maturation, and synaptic connectivity, particularly in the hippocampus, a region critical for learning and memory. It also reduces glycogen synthase kinase-3β (GSK3β) activity, which decreases tau hyperphosphorylation and Aβ production, key pathological features of AD. In 3xTg-AD mice, P-21 administered at 500 nmol/kg daily (via oral gavage or subcutaneous injection) for 3–12 months prevented synaptic deficits, enhanced neurogenesis, and reversed cognitive impairment by boosting markers like PSD-95 (postsynaptic density protein) and CREB (cAMP response element-binding protein).

Additionally, P-21 may modulate appetite by stimulating alpha-melanocyte-stimulating hormone (α-MSH) synthesis, potentially reducing food intake, though direct evidence is limited. Its effects on synaptic plasticity involve increased expression of synapsin, PSD-95, and MAP2, which regulate neurotransmitter release, synaptic organization, and dendritic stability, respectively. These mechanisms make P-21 a candidate for studying neurodegenerative diseases and cognitive enhancement in preclinical models.

Benefits of Using P-21

P-21’s potential benefits, based on preclinical studies in murine models and in vitro research, include:

• Enhanced Neurogenesis: Promotes proliferation and differentiation of neural progenitor cells in the hippocampal dentate gyrus, increasing new neuron formation and integration into neural networks, as shown in 3xTg-AD mice.

• Improved Cognitive Function: Enhances learning, short-term memory, and spatial reference memory in normal and AD-model mice, potentially through increased BDNF and CREB activity.

• Neuroprotection: Reduces tau hyperphosphorylation and Aβ plaque accumulation, slowing AD progression in transgenic models, and protects neurons from inflammatory damage.

• Synaptic Plasticity: Increases expression of synaptic markers (synapsin, PSD-95, MAP2), supporting neurotransmitter release, synaptic organization, and dendritic stability, critical for memory and learning.

• Reduced Neuroinflammation: Decreases glial fibrillary acidic protein (GFAP) levels, indicating reduced neuroinflammation in AD models, potentially mitigating neuronal damage.

• Potential Appetite Regulation: May reduce food intake via α-MSH stimulation, though evidence is preliminary and requires further investigation.

Limitations include the lack of human clinical trials, potential side effects like tiredness, and variability in dosing across studies (e.g., 289–500 mcg/kg in rats). Misformulations by some vendors (e.g., incorrect alanine-glycine sequences) have also raised concerns about product quality. P-21 remains a research compound, and its use in humans is prohibited due to unestablished safety profiles.

Certificate of Analysis

P-21 10mg – COA – FYP

The following technical details outline the properties of P-21 10mg, providing a scientific snapshot of the peptide.