P21 / P-021 (CNTF mimetic) (5mg)

P21 is a small synthetic peptide designed by Iqbal's group (NYU) as a CNTF mimetic. It acts as an agonist of the CNTFR-α/LIFR/gp130 complex, activating JAK2-STAT3 signaling without the toxic side effects of full-length CNTF (which was halted in Phase 3 for ALS due to cachexia). In animal models, it increases BDNF and NT-3 levels in the hippocampus, enhances the survival of newborn neurons in the dentate gyrus, reduces tau protein phosphorylation via GSK-3β inhibition, and improves spatial memory in transgenic Alzheimer's models (3xTg-AD, APP/PS1). Translation to humans remains **entirely hypothetical**.

• Reconstitution: 2.5 mL bacteriostatic water → 2 mg/mL.
• Status: Pure research peptide — NO human clinical data.
• Preclinical doses: In mice ~30–60 nmol/kg SC or i.p.
• No human dose equivalent — extrapolations are speculative.
• Storage: 2–8 °C after reconstitution.

1. Clean the stoppers with an alcohol pad.
2. Withdraw 2.5 mL of bacteriostatic water.
3. Inject slowly against the wall of the vial.
4. Gently swirl until dissolved — do not shake.
5. Store at 2–8 °C, protect from light.

• P21 is derived from region 148–151 of CNTF (region D1).
• Crosses the blood-brain barrier in animal models (mice).
• In preclinical studies, it enhances BDNF, NT-3, and neurogenesis in the hippocampus.
• In Alzheimer's models (3xTg-AD), it reduces tau pathology and improves learning.
• No Phase 1 clinical trial in humans has been initiated to date.

• Preclinical studies in mice: 30–60 nmol/kg, i.p. or SC.
• Duration of administration: 2 weeks to 12 months (aging models).
• No validated human dosing protocol.
• No information on human pharmacokinetics.
• Use only in approved research protocols/IACUC.
• Break between cycles: A 2–4 week break is recommended before repeating the cycle.

• Lyophilized powder: −20 °C or 2–8 °C.
• Reconstituted: 2–8 °C, use within 7–14 days.
• Freeze in aliquots for long-term storage (−80 °C).

• Research reagent — not for human use.
• No evidence of safety/efficacy in humans.
• Not available through approved pharmaceutical channels.
• Neuroprotection claims originate exclusively from animal models.
• This protocol is strictly educational/investigational.

1. P-021 design and CNTF mimicry — Blanchard J, Wanka L, Iqbal K, et al. A mimetic peptide of CNTF rescues spatial learning. Brain Res. 2010.
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2. P-021 in 3xTg-AD mice — Kazim SF, Iqbal K. Neurotrophic factor small-molecule mimetics mediated neuroregeneration in Alzheimer's disease. Mol Neurodegener. 2016.
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3. P21 and adult hippocampal neurogenesis — Bolognin S, et al. An experimental rat model of sporadic AD and rescue of cognitive impairment with a neurotrophic peptide. Acta Neuropathol. 2014.
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4. Tau pathology rescue — Khatoon S, Chalbot S, Bolognin S, Puoliväli J, Iqbal K. Elevated tau level in aged rat CSF reduced by treatment with a neurotrophic peptide P021. J Alzheimers Dis. 2015.
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5. Review — peptidomimetics for AD — Iqbal K, et al. Peptidomimetics as potential therapeutics for Alzheimer's disease. Curr Alzheimer Res. 2018.
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