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What Is Pinealon? The Tripeptide Glu-Asp-Arg in Neuronal and Pineal Research

What Is Pinealon? The Tripeptide Glu-Asp-Arg in Neuronal and Pineal Research

Pinealon is the trade name given to a synthetic tripeptide with the sequence glutamic acid-aspartic acid-arginine, abbreviated Glu-Asp-Arg or EDR, one of a family of short peptides developed out of a decades-long Russian research program on tissue-specific peptide bioregulators. The broader program, its history and its best-known members are covered in bioregulator peptides explained; this article stays narrowly on Pinealon itself: what the EDR sequence is, which laboratories have studied it, and what specific outcomes their cell-culture and rodent experiments reported. Most of the published work on EDR comes from the St. Petersburg Institute of Bioregulation and Gerontology and collaborating Russian university groups, working in organotypic tissue culture and in aged or stressed rodent models rather than in human trials.

AttributeDetail
NamePinealon, synthetic tripeptide
SequenceGlu-Asp-Arg (EDR), three amino acids
ClassShort peptide bioregulator, part of the Khavinson peptide series
What studies examineSignaling molecule expression in pineal cell culture, serotonin-pathway gene regulation, hypoxia and hypothermia neurochemistry, learning-task performance in aged rats
Model systems usedOrganotypic pineal gland culture, cultured brain cortex cells, aged rats under hypobaric hypoxia or mild hypothermia
Form suppliedLyophilized powder, research use only

What is the Glu-Asp-Arg sequence, and where does it fit among the short peptide bioregulators?

EDR is one of several very short peptides, most two to four amino acids long, that came out of the same research program as the tetrapeptide Ala-Glu-Asp-Gly and the dipeptide Lys-Glu. Each of these peptides was associated with a different tissue in the original research program, and EDR in particular has been studied for effects on neuronal and pineal gland tissue rather than immune or vascular tissue, which is why it carries the Pinealon name. The bioregulator peptides explained article covers how this naming and tissue-association scheme works across the wider peptide family; the sections below focus only on what has actually been published about the EDR sequence itself.

What has organotypic pineal cell culture research examined?

One of the earliest published characterizations of EDR examined its effect on signaling molecule expression directly in organotypic pineal gland culture taken from three-month-old rats, alongside three related peptides. In that work, EDR did not change expression of the apoptosis marker AIF in pinealocytes, in contrast to a related tetrapeptide, which stimulated a transcription factor tied to pinealocyte secretory activity. The proliferative marker Ki-67 was likewise stimulated by two other peptides in the comparison set but not by EDR, indicating that EDR's activity profile in pineal tissue is distinct from, and narrower than, some of the other short peptides tested alongside it in the same culture system (Khavinson et al., 2011).

What has research examined in cultured brain cortex cells?

A separate line of work looked at aging cultures of brain cortex cells and reported that EDR, together with the tripeptide Lys-Glu-Asp, stimulated expression of serotonin in these cultures. The same study used a molecular docking method to show that both peptides could interact with a nucleotide sequence in the gene encoding tryptophan hydroxylase, the enzyme responsible for the first step of serotonin synthesis, proposing an epigenetic mechanism for the peptides' effect on serotonin production in aging cortical tissue (Khavinson et al., 2014).

What have aged-rat hypoxia and hypothermia studies reported?

A series of experiments from a research group at Southern Federal University tested Pinealon against a comparator peptide preparation, Cortexin, in 18-month-old rats exposed to acute hypobaric hypoxia or mild hypothermia. Pinealon administration was associated with a smaller effect on free-radical processes and caspase-3 activity in the brain than Cortexin, while both preparations were linked to changes in brain adrenergic mediator and cortical serotonin content under the two stress models (Mendzheritsky et al., 2015). A related paper from the same group, using the acute hypoxia model specifically, reported that Pinealon was associated with markers consistent with increased neurogenesis and a decrease in neuroinflammatory markers toward reference levels in old rat brains, whereas Cortexin's effect pattern centered more on programmed cell death markers and interleukin-6 (Mendzheritskiĭ et al., 2014). A third study from this group, testing learning performance in a Morris water maze alongside caspase-3 measurements in brain structures of rats of different ages, reported that Pinealon had a more favorable effect on maze learning in both young and old animals than Cortexin did in the same experiment (Mendzheritski et al., 2013).

What has research examined in relation to Alzheimer's disease pathology?

A 2020 paper focused specifically on possible molecular mechanisms behind EDR's effects on gene expression and protein synthesis in the context of Alzheimer's disease pathogenesis, reviewing and extending earlier organotypic and cell-culture findings into a proposed gene-regulatory framework for how the peptide might influence neuronal gene activity relevant to that disease process (Khavinson et al., 2020). This paper sits alongside, rather than replacing, the cell-culture and rodent work described above; it is a mechanistic and review-style contribution rather than a new animal experiment, and like the rest of the literature on EDR, it describes laboratory and modeling work, not a clinical study in people.

How does Pinealon compare with other short peptides studied for vascular or neuronal signaling?

Within the same research program, the tripeptide Lys-Glu-Asp, sold under the name Vesugen, has been studied for a distinct set of effects centered on vascular endothelium rather than pineal or cortical tissue, though the two peptides have appeared together in some of the same cell-culture experiments described above; see what is Vesugen for that peptide's own literature. Researchers working with this peptide family generally treat sequence, tissue association and experimental readout as distinct variables, so results for one short peptide should not be assumed to generalize to another even when the peptides were tested in the same publication.

Handling notes

Pinealon is supplied as a lyophilized powder intended for laboratory research use. As with other short peptides, it should be stored according to the certificate of analysis and reconstituted using standard bench technique; see peptide half-life explained for background on why prompt, cold-chain-conscious handling after reconstitution matters for a given research timeline. Before using any lot in an assay, confirm identity and purity against its certificate of analysis; how to read a peptide certificate of analysis walks through what each section of that document reports. Lot-specific specifications for research-grade Pinealon are posted on our Pinealon lot page.

Frequently asked questions

What sequence does Pinealon contain?

Pinealon is a synthetic tripeptide with the sequence glutamic acid-aspartic acid-arginine, written Glu-Asp-Arg or abbreviated EDR in the primary literature.

Is Pinealon the same compound as Epithalon or Thymalin?

No. Pinealon, Epithalon and Thymalin come from the same short-peptide bioregulator research program but are chemically distinct: Pinealon is the EDR tripeptide, Epithalon is the AEDG tetrapeptide, and Thymalin is a peptide complex rather than a single synthetic sequence. See bioregulator peptides explained for how the family is organized.

What model systems have published studies used for Pinealon?

Published work has used organotypic pineal gland culture, cultured aging brain cortex cells, and aged rats under acute hypobaric hypoxia or mild hypothermia, with outcomes including caspase-3 activity, cytokine levels, learning-task performance and neurotransmitter content.

Has Pinealon been studied in humans?

The published literature identified for EDR consists of cell-culture and rodent studies, along with a mechanistic review discussing gene-expression pathways relevant to Alzheimer's disease. This article summarizes laboratory research models, not clinical evidence, and nothing here describes a protocol for use in any subject.

How does Pinealon differ from Cortexin in the rat studies described above?

Across several comparative rat experiments, Pinealon and Cortexin produced different effect patterns on the same measures. Cortexin showed a larger effect on free-radical processes and caspase-3 activity in some studies, while Pinealon showed more favorable effects on maze-learning performance and markers associated with neurogenesis in others. The two preparations are structurally different and should not be treated as interchangeable based on these comparisons.

How is Pinealon supplied for laboratory use?

As a lyophilized powder intended for research use only, sold by lot with an accompanying certificate of analysis.

References

  1. Khavinson VKh, Linkova NS, Chalisova NI, Dudkov AV, Koncevaya EA. Effect of short peptides on expression of signaling molecules in organotypic pineal cell culture. Bull Exp Biol Med. 2011;152(1):138-141. PubMed 22803060.
  2. Khavinson VKh, Lin'kova NS, Tarnovskaya SI, Umnov RS, Elashkina EV, Durnova AO. Short peptides stimulate serotonin expression in cells of brain cortex. Bull Exp Biol Med. 2014;157(1):77-80. PubMed 24909721.
  3. Mendzheritsky AM, Karantysh GV, Ryzhak GA, Prokofiev VN. Pinealon and Cortexin influence on behavior and neurochemical processes in 18-month aged rats within hypoxia and hypothermia. Adv Gerontol. 2015;28(3):532-539. PubMed 28509493.
  4. Mendzheritskiĭ AM, Karantysh GV, Ryzhak GA, Dem'ianenko SV. Regulation of content of cytokines in blood serum and of caspase-3 activity in brains of old rats in model of sharp hypoxic hypoxia with Cortexin and Pinealon. Adv Gerontol. 2014;27(1):94-97. PubMed 25051764.
  5. Mendzheritski AM, Karantysh GV, Abramchuk VA, Ryzhak GA. Effect of peptide geroprotectors on the navigation system learning and caspase-3 in brain structures in rats of different age. Adv Gerontol. 2013;26(2):252-257. PubMed 28976148.
  6. Khavinson V, Linkova N, Kozhevnikova E, et al. EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's Disease. Molecules. 2020;26(1):1058. PubMed 33396470.

Research use only. Homegrown Peptides products are for laboratory research and are not for human or animal use. Nothing in this article is medical advice.

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