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preclinicalCognitive & Neuro

Colivelin

Also known as: ADNF-9-humanin hybrid peptide, AGA-(C8R)HNG17 hybrid peptide, SALLRSIPA-CLRQDSYDLG

Colivelin is a synthetic hybrid neuroprotective peptide created by fusing activity-dependent neurotrophic factor 9 (ADNF-9, also known as SAL) with a potent humanin derivative (AGA-(C8R)HNG17). This dual-action peptide activates both the ADNF/ADNP-mediated and humanin/STAT3-mediated neuroprotective pathways simultaneously, providing synergistic protection against Alzheimer's disease-related neurotoxicity. In preclinical studies, Colivelin demonstrates significantly greater neuroprotective potency than either of its parent peptides alone, protecting against amyloid-beta toxicity, presenilin mutation-induced cell death, and memory impairment in Alzheimer's disease mouse models.

3 cited references·5 researched benefits

Quick Answer

Colivelin is a synthetic hybrid neuroprotective peptide combining ADNF-9 and a humanin derivative to activate two independent neuroprotective signaling pathways simultaneously. It protects neurons against amyloid-beta toxicity and presenilin-mutation-induced cell death, and reverses memory impairment in Alzheimer's disease mouse models with greater potency than either parent peptide alone. Colivelin signals through both STAT3 and ADNP-dependent pathways, representing a unique dual-mechanism approach to neurodegeneration.

Key Facts

Mechanism
Colivelin activates two distinct and complementary neuroprotective signaling pathways. The humanin-derived portion (AGA-(C8R)HNG17) binds to the IL-27 receptor/CNTFR/gp130 tripartite receptor complex, activating the JAK2/STAT3 signaling cascade. STAT3 activation upregulates anti-apoptotic genes (Bcl-2, Bcl-xL) and suppresses pro-apoptotic signaling, directly counteracting amyloid-beta-induced and presenilin-mutation-induced neuronal death. The ADNF-9 (SAL) portion activates a separate pathway mediated by activity-dependent neuroprotective protein (ADNP), which is essential for brain development and function. ADNP acts through the SWI/SNF chromatin remodeling complex to regulate gene expression patterns critical for neuronal survival. By engaging both pathways simultaneously, Colivelin provides synergistic neuroprotection — if one pathway is blocked (e.g., by dominant-negative STAT3), the other pathway can still maintain partial protection, making it more robust than single-mechanism approaches.
Research Status
preclinical
Half-Life
Not established in humans (preclinical compound)
Molecular Formula
C₁₂₃H₂₀₂N₃₈O₃₈S₁
Primary Use
Cognitive & Neuro
Table of Contents

Benefits

  • Superior neuroprotection against amyloid-beta — prevents neuronal death caused by amyloid-beta 1-42 and amyloid-beta 1-43 peptides at lower concentrations than either ADNF-9 or humanin alonepreliminary
  • Protection against presenilin-mutation toxicity — rescues neurons from cell death caused by familial Alzheimer's disease presenilin mutations (V642I-APP, M146L-PS1, N141I-PS2)preliminary
  • Memory impairment reversal — intracerebroventricular administration reverses spatial memory deficits caused by amyloid-beta injection in mouse modelspreliminary
  • Dual-pathway neuroprotection — activates both STAT3 and ADNP pathways, providing redundant protection even when one pathway is pharmacologically blockedmoderate
  • Potency advantage — effective at nanomolar concentrations in vitro, demonstrating significantly higher potency than the parent peptides when tested individuallypreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Intracerebroventricular (preclinical)1–10 nmol (animal dosing)Single or repeated injections in research protocolsNo human dosing has been established. Preclinical studies used intracerebroventricular injection, which is not practical for therapeutic use. Development of peripherally-administered formulations would be necessary for clinical application.
Intranasal (theoretical)Not establishedNot establishedIntranasal delivery is being explored for brain-targeted peptide therapeutics and could potentially be a viable route for Colivelin, but no published studies have evaluated this route.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Unknown human side effects — no human clinical trials have been conducted; all safety data derives from cell culture and animal studiesserious
  • Theoretical immune modulation — activation of STAT3 signaling is involved in immune regulation and could theoretically alter immune function with chronic administrationrare
  • Theoretical oncogenic risk — STAT3 is a known oncogene when constitutively activated; long-term TrkB and STAT3 co-activation could theoretically promote tumor development, though this has not been observed in preclinical studiesrare

Frequently Asked Questions

How does Colivelin relate to humanin?
Colivelin is a hybrid peptide that incorporates a modified humanin sequence (AGA-(C8R)HNG17) as one of its two active domains. Humanin is a 24-amino acid mitochondria-derived peptide discovered in 2001 that protects against Alzheimer's-related neurotoxicity through STAT3 signaling. Colivelin enhances this by adding the ADNF-9 sequence, creating a dual-mechanism peptide that activates both humanin's STAT3 pathway and ADNF-9's ADNP pathway simultaneously. This synergistic design makes Colivelin more potent and more resistant to pathway-specific blockade than humanin alone.
Could Colivelin be used to treat Alzheimer's disease?
Colivelin shows therapeutic promise for Alzheimer's disease in preclinical models, but significant hurdles remain before clinical use. The primary challenges are: development of a practical delivery route (current studies use intracerebroventricular injection, which requires brain surgery); demonstration of blood-brain barrier penetration with peripheral administration; completion of toxicology and safety studies; and Phase I/II/III clinical trials. The peptide's mechanism — targeting amyloid-beta toxicity and presenilin-mediated pathology — addresses core Alzheimer's pathology, but decades of Alzheimer's drug failures demonstrate how difficult it is to translate preclinical promise into clinical efficacy.
Is Colivelin available for purchase?
Colivelin can be obtained through specialty peptide synthesis companies for research purposes only. It is not available as a pharmaceutical product or dietary supplement anywhere in the world. Custom synthesis is expensive due to the peptide's length and complexity. Researchers typically obtain it from peptide synthesis services with verified purity (>95% by HPLC). It should not be used for human self-experimentation as it has no established safety profile in humans.
What is ADNF-9 and why was it combined with humanin?
ADNF-9 (also called SAL, sequence SALLRSIPA) is a 9-amino acid peptide derived from activity-dependent neurotrophic factor, discovered by Illana Bhoshen at NIH. It protects neurons through a pathway mediated by activity-dependent neuroprotective protein (ADNP). Researchers at Keio University combined it with humanin because the two peptides protect neurons through entirely independent signaling pathways — if one pathway is blocked or insufficient, the other can compensate. This "belt and suspenders" approach to neuroprotection was validated when experiments showed that Colivelin maintained protection even when STAT3 was pharmacologically inhibited.

References

  1. 1
    Colivelin, a novel humanin derivative, activates both the STAT3 and the ADNP/ADNF neuroprotective pathways to prevent Alzheimer's disease-related neurotoxicity(2004)PubMed ↗
  2. 2
    Colivelin rescues neurons from intracellular amyloid-beta 1-42-induced toxicity and memory impairment in mice(2007)PubMed ↗
  3. 3
    Humanin and colivelin: neuroprotective peptides from the mitochondrial genome targeting Alzheimer's disease pathology(2010)PubMed ↗

Latest Research

Last updated: 2026-02-19