Genes That Associated with Action of ACTH-like Peptides with Neuroprotective Potential in Rat Brain Regions with Different Degrees of Ischemic Damage.

Filippenkov IB, Shpetko YY, Ales DA, Stavchansky VV, Denisova AE, Yuzhakov VV, Fomina NK, Gubsky LV, Andreeva LA, Myasoedov NF, Limborska SA, Dergunova LV

International journal of molecular sciences28 Jun 2025Cited by 1 (Europe PMC)

PMID40650034PMCIDPMC12249733DOI10.3390/ijms26136256PepBankPUB-40650034

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Summary

In the treatment of ischemic stroke, an innovative approach is the use of neuroprotective compounds. Natural peptides, including adrenocorticotropic hormone (ACTH), can serve as the basis for such drugs. Previously, a significant effect of non-hormonal ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP peptides on the functions of the nervous system was shown. Also, while using RNA-Seq, we firstly revealed differentially expressed genes (DEGs) that associated with peptides in the penumbra-associated region of the frontal cortex (FC) of rats at 24 h after transient middle cerebral artery occlusion (tMCAO) model. Peptides significantly reduced profile disturbances caused by ischemia for almost two-thousand DEGs in FC related to the neurotransmitter and inflammatory response. Here, we studied how peptides affected the expression of genes in the striatum with an ischemic focus, predominantly. The same animals from which we previously acquired FC were used to collect striatum samples. Peptides generated fewer DEGs in the striatum than in the FC. Both peptides tended to normalize the profile of disturbances caused by ischemia for hundreds of DEGs, whereas 152 genes showed an even more affected profile in the striatum under ACTH(6-9)PGP action. These DEGs were associated with inflammation, predominantly. About hundred genes were overlapped between both peptides in both tissues and were associated with neuroactive ligand-receptor interaction, predominantly. Thus, genes that are associated with the ACTH-like peptide action in rat brain regions with varying levels of ischemia injury were identified. Moreover, differential spatial regulation of the ischemia process in the rat brain at the transcriptome levels was discovered under peptides with different ACTH structures. We suppose that our results may be useful for selecting more effective neuroprotective drug structures in accordance with their specific tissue/damage therapeutic impact.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

1 result from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Mechanism
In rats with tMCAO ischemia, Semax tended to normalize the ischemia-disturbed striatal expression profile of hundreds of differentially expressed genes.
In plain wordsIn rats with stroke-like brain injury, Semax tended to return the activity of hundreds of disturbed striatal genes toward normal.
Peptide
Semax
Outcome
MixedIschemia-disturbed gene expression profile in striatum
Study
ratn: not reported in source
transient middle cerebral artery occlusion (tMCAO) model, striatum
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Both peptides tended to normalize the profile of disturbances caused by ischemia for hundreds of DEGs
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we studied how peptides affected the expression of genes in the striatum with an ischemic focus, predominantly.
Show in the study text Report a problemFND-4065003401

Studies that did not test the peptide alone2

In this study, Semax was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Semax.

02AnimalNot a test of Semax aloneAnimal study (in vivo)Mechanism
In rats with tMCAO ischemia, the peptides, including Semax, generated fewer differentially expressed genes in the striatum than in the frontal cortex.
In plain wordsIn rats with stroke-like brain injury, the peptides changed fewer genes in the striatum than in the frontal cortex.
Peptide
Semax
Outcome
Not applicableNumber of differentially expressed genes, striatum versus frontal cortex
Study
ratn: not reported in source
transient middle cerebral artery occlusion (tMCAO) model, striatum
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
Peptides generated fewer DEGs in the striatum than in the FC.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we studied how peptides affected the expression of genes in the striatum with an ischemic focus, predominantly.
In this study, Semax was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semax.
Show in the study text Report a problemFND-4065003402
03AnimalNot a test of Semax aloneAnimal study (in vivo)Mechanism
In rats with tMCAO ischemia, about one hundred genes overlapped between Semax and ACTH(6-9)PGP in both tissues, mainly in neuroactive ligand-receptor interaction.
In plain wordsIn rats with stroke-like brain injury, about one hundred genes changed with both peptides in both brain areas, mostly linked to nerve signalling.
Peptide
Semax
Outcome
Not applicableGenes shared by both peptides in both tissues
Study
ratn: not reported in source
transient middle cerebral artery occlusion (tMCAO) model, striatum
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
About hundred genes were overlapped between both peptides in both tissues and were associated with neuroactive ligand-receptor interaction, predominantly.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we studied how peptides affected the expression of genes in the striatum with an ischemic focus, predominantly.
In this study, Semax was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semax.
Show in the study text Report a problemFND-4065003403

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
9 Oct 2026, 19:08 UTC
Study results updated
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

Subjects

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