P21 is a CNTF-derived synthetic peptide designed for stability and BBB permeability to promote neurogenesis, memory, and neuroprotection. It may elevate BDNF, enhance hippocampal neurogenesis, and reduce amyloid/tau pathology.
P21
Also known as: Neurotrophic Peptide P21; CNTF Analog
Overview
Benefits
- Cognitive enhancement
- Alzheimer’s support
- Stroke recovery
- Eye health
- Appetite control
Consider This Peptide If You Want To
- Enhance memory, learning, and brain plasticity
- Support nerve regeneration and neuroprotection
Dosage & Administration
Dosage Guidelines
Recommended Dosage
• Amount:10 mg
• Frequency:daily
• Duration:8 weeks
• Rest Period:8 weeks
• Time of Day:morning
• Ingestion:subcutaneous
Administration Routes:SubcutaneousIntramuscularOral
Research Findings on Dosage:
Common Dosage Forms
• Injection: Subcutaneous or intramuscular.
• Oral: Capsule form for systemic absorption.
Commonly Reported Dosage
• Neuroprotection and Cognitive Support:
◦ Initial dose: 10--20 mg daily, subcutaneous or oral.
◦ Duration: 4--12 weeks, assess response and titrate as needed.
• Neurodegenerative Diseases (e.g., Alzheimer's):
◦ Maintenance dose: 15--30 mg daily for up to six months.
• Appetite Regulation and Satiety:
◦ 10--15 mg daily in preclinical studies; human trials pending.
Mechanism of Action
Mechanism of Action
How this peptide works in the body
Neurogenesis:
P21 enhances the proliferation of neural progenitor cells in the hippocampus, particularly within the dentate gyrus, by upregulating brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF). It promotes neuronal differentiation via ERK and CREB signaling, leading to improved cognitive function and neuroprotection.
Anti-Amyloid and Tau Activity:
P21 suppresses beta-secretase 1 (BACE1) activity, reducing amyloid-beta (Aβ) plaque formation, a hallmark of Alzheimer's disease. It also inhibits tau hyperphosphorylation by modulating glycogen synthase kinase-3 beta (GSK-3β) and cyclin-dependent kinase 5 (CDK5), preserving microtubule integrity and neuronal structure.
Synaptic Plasticity:
P21 restores synaptic function by enhancing NMDA receptor activity and dendritic spine density in cognitively impaired brains. It activates the cAMP/protein kinase A (PKA) pathway, strengthening long-term potentiation (LTP)and improving memory consolidation.
Inflammation Modulation:
P21 reduces neuroinflammation by downregulating pro-inflammatory cytokines (IL-1β, TNF-α) while increasing anti-inflammatory cytokines (IL-10, TGF-β). It also suppresses microglial activation and oxidative stress, protecting neurons from inflammatory-mediated damage.
Consider Stacking With
- Semax
Side Effects & Cautions
Common Side Effects
- Mild nervousness or irritability
Cautions
- Overstimulation of neurogenesis (dose-related)
- Local redness/irritation if injected
Research & References
Research Highlights
Cognitive Restoration in Alzheimer's Models:
Improved memory and learning in 3xTg-AD mice.
Reduced amyloid beta and tau accumulation, with restored synaptic function.
Neurogenesis in Aging Models:
Increased hippocampal progenitor proliferation and differentiation in aged Fisher rats.
Stroke Recovery:
Enhanced motor function and neurogenesis up to ten weeks post-stroke in animal studies.
Macular Degeneration:
Prevented photoreceptor degeneration and reduced pathological changes in aged models.
References
Li, B., Wanka, L., Blanchard, J., et al. (2010). Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice. FEBS Letters
Baazaoui, N., & Iqbal, K. (2017). Prevention of dendritic and synaptic deficits and cognitive impairment with a neurotrophic compound. Alzheimer's Research & Therapy
Liu, Y., Wei, W., Baazaoui, N., et al. (2019). Inhibition of AMD-like pathology with a neurotrophic compound in aged rats and 3xTg-AD mice. Frontiers in Aging Neuroscience
Khatoon, S., Chalbot, S., Bolognin, S., et al. (2015). Elevated tau level in aged rat cerebrospinal fluid reduced by treatment with a neurotrophic compound. Journal of Alzheimer's Disease