Enduring Effects of Humanin on Mitochondrial Systems in TBI Pathology.

Thapak P, Ying Z, Gomez-Pinilla F

Biomolecules6 Dec 2025Cited by 3 (Europe PMC)

PMID41463361PMCIDPMC12730897DOI10.3390/biom15121705PepBankPUB-41463361

Summary

Traumatic brain injury has long-term detrimental effects on neurological function and general quality of life of affected individuals. Bioenergetic failure is a primary mechanism for cellular dysfunction. We used the mitochondrial activator humanin (HN) to try to normalize the disruptive action of TBI on cellular bioenergetics in the hippocampus. We found that HN supplied right after the injury counteracted the action of TBI on metabolic sensing proteins (LKB1, AMPK, and AKT). HN also counteracted cognitive function and restored the synaptic proteins (Synapsin I and PSD-95) at three weeks post-injury. Moreover, HN normalized the disruptive action of TBI on mitochondrial functioning and dynamics (fusion, fission, and mitophagy). In addition, HN treatment counteracted TBI's effects on mitochondrial biogenesis (PGC-1α), antioxidant (SOD2), and apoptotic marker (CC3). Furthermore, HN intervention in injured animals counteracted the gene expression linked with inflammation (Itgax, SALL1, GFAP, and NLRP3), synaptic plasticity (HDAC2), and bioenergetics (mtND2, TFAM, SIRT1, and SIRT3). These observations emphasize the therapeutic potential of HN by normalizing the fundamental aspects of TBI pathogenesis central to cellular bioenergetics and synaptic plasticity.

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

Results from this study10

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

01AnimalAnimal study (in vivo)Mechanism
In injured animals, HN given right after traumatic brain injury counteracted the injury's action on the metabolic sensing proteins LKB1, AMPK and AKT.
In plain wordsIn injured animals, Humanin given right after brain injury countered the injury's effect on energy-sensing proteins.
Peptide
Humanin
Outcome
Direction not reportedMetabolic sensing proteins (LKB1, AMPK, AKT) after TBI
Study
n: not reported in source
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
HN supplied right after the injury counteracted the action of TBI on metabolic sensing proteins (LKB1, AMPK, and AKT).
1 context sentence(design, population, supporting numbers)
Summary · context
We used the mitochondrial activator humanin (HN) to try to normalize the disruptive action of TBI on cellular bioenergetics in the hippocampus.
Show in the study text Report a problemFND-4146336101
02AnimalAnimal study (in vivo)Efficacy outcome
In injured animals, HN counteracted the effect of traumatic brain injury on cognitive function at three weeks post-injury.
In plain wordsIn injured animals, Humanin countered the effect of brain injury on cognitive function.
Peptide
Humanin
Outcome
Direction not reportedCognitive function after TBI
Study
n: not reported in source
Outcome group
Cognition and memory · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
HN also counteracted cognitive function and restored the synaptic proteins (Synapsin I and PSD-95) at three weeks post-injury
1 context sentence(design, population, supporting numbers)
Summary · context
We used the mitochondrial activator humanin (HN) to try to normalize the disruptive action of TBI on cellular bioenergetics in the hippocampus.
Show in the study text Report a problemFND-4146336102
03AnimalAnimal study (in vivo)Mechanism
In injured animals, HN restored the synaptic proteins Synapsin I and PSD-95 at three weeks post-injury.
In plain wordsIn injured animals, Humanin restored two proteins that support nerve connections.
Peptide
Humanin
Outcome
IncreaseSynaptic proteins Synapsin I and PSD-95
Study
n: not reported in source
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
restored the synaptic proteins (Synapsin I and PSD-95) at three weeks post-injury
1 context sentence(design, population, supporting numbers)
Summary · context
We used the mitochondrial activator humanin (HN) to try to normalize the disruptive action of TBI on cellular bioenergetics in the hippocampus.
Show in the study text Report a problemFND-4146336103
04AnimalAnimal study (in vivo)Mechanism
In injured animals, HN normalized the disruptive action of traumatic brain injury on mitochondrial functioning and dynamics (fusion, fission and mitophagy).
In plain wordsIn injured animals, Humanin normalized brain injury's disruption of how mitochondria work and renew.
Peptide
Humanin
Outcome
Direction not reportedMitochondrial functioning and dynamics
Study
n: not reported in source
Outcome group
Mitochondrial function · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Moreover, HN normalized the disruptive action of TBI on mitochondrial functioning and dynamics (fusion, fission, and mitophagy).
1 context sentence(design, population, supporting numbers)
Summary · context
We used the mitochondrial activator humanin (HN) to try to normalize the disruptive action of TBI on cellular bioenergetics in the hippocampus.
Show in the study text Report a problemFND-4146336104
05AnimalAnimal study (in vivo)Mechanism
In injured animals, HN treatment counteracted the effects of traumatic brain injury on mitochondrial biogenesis (PGC-1α).
In plain wordsIn injured animals, Humanin countered brain injury's effect on the making of new mitochondria.
Peptide
Humanin
Outcome
Direction not reportedMitochondrial biogenesis (PGC-1α)
Study
n: not reported in source
Outcome group
Mitochondrial function · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
counteracted TBI's effects on mitochondrial biogenesis (PGC-1α)
1 context sentence(design, population, supporting numbers)
Summary · context
We used the mitochondrial activator humanin (HN) to try to normalize the disruptive action of TBI on cellular bioenergetics in the hippocampus.
Show in the study text Report a problemFND-4146336105
06AnimalAnimal study (in vivo)Mechanism
In injured animals, HN treatment counteracted the effects of traumatic brain injury on the antioxidant SOD2.
In plain wordsIn injured animals, Humanin countered brain injury's effect on an antioxidant enzyme.
Peptide
Humanin
Outcome
Direction not reportedAntioxidant SOD2
Study
n: not reported in source
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
antioxidant (SOD2), and apoptotic marker (CC3).
1 context sentence(design, population, supporting numbers)
Summary · context
We used the mitochondrial activator humanin (HN) to try to normalize the disruptive action of TBI on cellular bioenergetics in the hippocampus.
Show in the study text Report a problemFND-4146336106
07AnimalAnimal study (in vivo)Mechanism
In injured animals, HN treatment counteracted the effects of traumatic brain injury on the apoptotic marker CC3.
In plain wordsIn injured animals, Humanin countered brain injury's effect on a marker of cell death.
Peptide
Humanin
Outcome
Direction not reportedApoptotic marker CC3
Study
n: not reported in source
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
apoptotic marker (CC3).
1 context sentence(design, population, supporting numbers)
Summary · context
We used the mitochondrial activator humanin (HN) to try to normalize the disruptive action of TBI on cellular bioenergetics in the hippocampus.
Show in the study text Report a problemFND-4146336107
08AnimalAnimal study (in vivo)Mechanism
In injured animals, HN intervention counteracted the gene expression linked with inflammation (Itgax, SALL1, GFAP and NLRP3).
In plain wordsIn injured animals, Humanin countered brain injury's changes in genes linked to inflammation.
Peptide
Humanin
Outcome
Direction not reportedInflammation-linked gene expression (Itgax, SALL1, GFAP, NLRP3)
Study
n: not reported in source
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Furthermore, HN intervention in injured animals counteracted the gene expression linked with inflammation (Itgax, SALL1, GFAP, and NLRP3), synaptic plasticity (HDAC2), and bioenergetics (mtND2, TFAM, SIRT1, and SIRT3).
1 context sentence(design, population, supporting numbers)
Summary · context
We used the mitochondrial activator humanin (HN) to try to normalize the disruptive action of TBI on cellular bioenergetics in the hippocampus.
Show in the study text Report a problemFND-4146336108
09AnimalAnimal study (in vivo)Mechanism
In injured animals, HN intervention counteracted the gene expression linked with synaptic plasticity (HDAC2).
In plain wordsIn injured animals, Humanin countered brain injury's change in a gene linked to nerve connection flexibility.
Peptide
Humanin
Outcome
Direction not reportedSynaptic plasticity gene HDAC2
Study
n: not reported in source
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Furthermore, HN intervention in injured animals counteracted the gene expression linked with inflammation (Itgax, SALL1, GFAP, and NLRP3), synaptic plasticity (HDAC2), and bioenergetics (mtND2, TFAM, SIRT1, and SIRT3).
1 context sentence(design, population, supporting numbers)
Summary · context
We used the mitochondrial activator humanin (HN) to try to normalize the disruptive action of TBI on cellular bioenergetics in the hippocampus.
Show in the study text Report a problemFND-4146336109
10AnimalAnimal study (in vivo)Mechanism
In injured animals, HN intervention counteracted the gene expression linked with bioenergetics (mtND2, TFAM, SIRT1 and SIRT3).
In plain wordsIn injured animals, Humanin countered brain injury's changes in genes linked to cell energy.
Peptide
Humanin
Outcome
Direction not reportedBioenergetics gene expression (mtND2, TFAM, SIRT1, SIRT3)
Study
n: not reported in source
Outcome group
Mitochondrial function · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Furthermore, HN intervention in injured animals counteracted the gene expression linked with inflammation (Itgax, SALL1, GFAP, and NLRP3), synaptic plasticity (HDAC2), and bioenergetics (mtND2, TFAM, SIRT1, and SIRT3).
1 context sentence(design, population, supporting numbers)
Summary · context
We used the mitochondrial activator humanin (HN) to try to normalize the disruptive action of TBI on cellular bioenergetics in the hippocampus.
Show in the study text Report a problemFND-4146336110

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
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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