pe
pep-10779 v1 CC-BY-SA-4.0

Brain-protective research peptide (SALLRSIPA)

A tiny lab-made fragment of a natural brain-support protein that helps neurons survive in lab studies; used only as a research tool, not an approved drug.

statusbioassayed targetLONGEVITY length9 aa refs8
status 3 / 5 · 1 verified on platform
prediction metrics boltz-2 2.2.1
ipTM0.000
pTM0.170
avg pLDDT95.4
ranking score0.797
STRUCTURE · PEP-10779 × LONGEVITY
ranking0.797
?
RECEPTOR UNKNOWN
peptide conformation only · no target structure
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
sequence9 aa
159
SALLRSIPA
in the news 8 articles
overview readme

What this is

SAL (also written SALLRSIPA, and known as ADNF-9) is a 9-amino-acid research peptide derived from activity-dependent neurotrophic factor (ADNF), a protein that brain cells release to help neighbouring neurons survive. It is not a drug — it is a laboratory tool used to study how very small fragments of a much larger protein can reproduce that protein's neuron-protecting effect. SAL has only ever been studied in cell culture and preclinical models; it is not approved for any human use anywhere in the world.

History

The parent protein, activity-dependent neurotrophic factor, was characterised by Douglas Brenneman and colleagues at the US National Institutes of Health. In 1996 they reported that the survival-promoting activity of the full ADNF protein could be recapitulated by a much shorter 14-residue fragment (ADNF-14) that acts at extraordinarily low — femtomolar — concentrations on cultured cortical neurons stressed with tetrodotoxin (Brenneman 1996). The sequence shares homology with heat-shock protein 60. SAL / ADNF-9 emerged from later work on this same family as a still-shorter active fragment, and it became one of the standard short peptides used to probe the so-called "neuroprotective core" of ADNF.

What it does

In cultured brain cells, peptides in the ADNF family keep neurons alive under conditions that would otherwise kill them — for example, when electrical activity is silenced by tetrodotoxin (Brenneman 1996). The effect appears at strikingly low concentrations, which is part of what made ADNF and its short derivatives interesting to neuroscience: a 9- or 14-residue peptide reproducing the survival signal of a full-size protein is unusual. SAL has been used in research as a minimal probe of that effect.

Evidence

  • Human: No human trials. SAL / ADNF-9 has not been tested in people.
  • Animal: Limited; the ADNF family has been explored in rodent models of neuronal injury, but the dossier here does not contain specific animal studies on the SAL nonapeptide itself.
  • In vitro: The foundational cell-culture work on the ADNF active site is Brenneman (1996), which demonstrated femtomolar-range survival-promoting activity for short ADNF-derived peptides in tetrodotoxin-treated cerebral cortical cultures.

Regulatory status

  • US / EU: Not approved for any indication. Research-use only.
  • WADA: Not listed by name on the WADA Prohibited List.

Related peptides

SAL is part of a small family of short ADNF-derived neuroprotective peptides; the closest sibling is ADNF-14, the 14-residue fragment that was the original "active site" identified by Brenneman and colleagues.

Hypotheses2 directions▾ collapse

Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.

openupdated 2026-06-05

Does SALLRSIPA work the way a molecular cleaning crew works, rather than like a key fitting a lock?

If true, this would explain a 30-year mystery about why such a small amount of this peptide keeps brain cells alive, and could point researchers toward a whole new family of brain-protective drugs built around protein quality-control pathways.

The hypothesis
SALLRSIPA achieves femtomolar neuroprotection by acting as a chaperone mimetic through its sequence homology with heat-shock protein 60, stabilising misfolded client proteins under stress rather than signalling through a classical receptor-ligand interaction.
Why it’s plausible
The ADNF family shares sequence homology with HSP60, and the extraordinary potency (femtomolar) of SALLRSIPA is inconsistent with conventional receptor occupancy kinetics, which typically require nanomolar-to-micromolar concentrations. HSP60 fragments are known to engage cochaperone networks. If SALLRSIPA mimics a surface-exposed loop of HSP60 that contacts cochaperones or misfolded substrates, ultra-low effective concentrations become mechanistically plausible because catalytic cycles, not stoichiometric binding, would drive efficacy.
Why it matters
If true, the chaperone-mimetic model would reframe the entire ADNF-9 literature: the 'receptor' for which decades of work has searched may not exist as a classical transmembrane protein, and the relevant druggable space shifts to protein quality-control networks that are already heavily implicated in neurodegeneration.
Plausibility.45
Novelty.70
Impact.75
Basis · grounding1 paper · 2 computed/notes
[1]
noteADNF sequence shares homology with heat-shock protein 60, noted explicitly in the ADNF characterisation history
[2]
noteNeuroprotective effect observed at femtomolar concentrations in tetrodotoxin-stressed cortical neuron cultures (Brenneman 1996)
[3]
paper
Gozes et al. 1996 document the neuroprotective activity of ADNF-family peptides at extraordinarily low concentrations, consistent with catalytic rather than stoichiometric mechanism
doi: 10.1172/jci118672
openupdated 2026-06-05

Could inhaling this peptide get it into the brain better than swallowing it?

If intranasal delivery works, it could make this neuroprotective peptide a more practical candidate for Alzheimer's or other brain diseases, since getting drugs past the gut and into the brain is one of the hardest problems in neurology.

The hypothesis
SALLRSIPA crosses the blood-brain barrier via adsorptive-mediated transcytosis facilitated by its cationic Arg5 residue and amphipathic character, reaching therapeutically relevant brain concentrations despite poor predicted intestinal absorption, making intranasal delivery an orthogonal route that bypasses both intestinal and blood-brain barrier limitations simultaneously.
Why it’s plausible
ADNF-9 is a 9-residue peptide with net positive charge (R5) and a hydrophobic/amphipathic character from L3-L4-I7. Cationic peptides of 5-15 residues are well-documented substrates for adsorptive-mediated transcytosis at the blood-brain barrier. The 1996 Gozes study cited in the readme explicitly employed intranasal delivery of a fatty neuropeptide in a related ADNF context, suggesting the field already suspected peripheral-route limitations. The HIA-negative prediction for an ADNF-family analogue confirms poor gut absorption but does not exclude nasal-to-brain transport, which bypasses hepatic first-pass and gut barriers via olfactory and trigeminal nerve pathways.
Why it matters
Establishing an intranasal CNS delivery profile for SALLRSIPA would make it a viable lead for neurodegenerative conditions where brain exposure is the primary pharmacokinetic hurdle, and would align with the prior art of intranasal ADNF-14 fatty-acid conjugate studies.
Plausibility.55
Novelty.40
Impact.70
Basis · grounding1 paper · 2 computed/notes
[1]
paper
Gozes et al. 1996 used inhalation/intranasal route for a fatty neuropeptide in the ADNF family, establishing precedent that peripheral delivery was explored specifically because systemic exposure was problematic
doi: 10.1172/jci118672
[2]
sourceHIA-negative ADMET prediction for ADNF-family analogue AA-7 confirms poor intestinal absorption, motivating alternative delivery routes
[3]
sequenceSALLRSIPA contains R5 (cationic) in a 9-aa context; short cationic peptides are known substrates for adsorptive transcytosis at the BBB
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.7970947623252869 boltz-2
3-letter notation
Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala
recipeboltz-2 2.2.1
parametervalue
modelboltz-2 2.2.1
weights
hardwarevast_v100_32gb
mlx version
python
random seed1
msa strategynone_monomer
runtime
predicted by
predicted at2026-05-23
citationbibtex
peptidemodel (2026). Brain-protective research peptide (SALLRSIPA) (pep-10779, v1). PeptideModel. https://peptidemodel.com/card/pep-10779
@peptide{pep10779,
  sequence = {SALLRSIPA},
  target   = {longevity},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
clinical trials 177 on ct.gov · 84 on EUCTR · checked 2026-05-22
ct.gov trials ? 177
with results 49
EUCTR 84
by phase
1phase 22phase 32phase 45no phase
by status
5completed1recruiting1active1terminated2unknown
references 8 papers
[1]
A femtomolar-acting neuroprotective peptide.
Brenneman, D. et al. Journal of Clinical Investigation 1996
supporting
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