Humanin Derivatives Inhibit Necrotic Cell Death in Neurons.

Cohen A, Lerner-Yardeni J, Meridor D, Kasher R, Nathan I, Parola AH

Molecular medicine (Cambridge, Mass.)4 Jun 2015Cited by 17 (Europe PMC)

PMID26062019PMCIDPMC4607621DOI10.2119/molmed.2015.00073PepBankPUB-26062019

Summary

Humanin and its derivatives are peptides known for their protective antiapoptotic effects against Alzheimer's disease. Herein, we identify a novel function of the humanin-derivative AGA(C8R)-HNG17 (namely, protection against cellular necrosis). Necrosis is one of the main modes of cell death, which was until recently considered an unmoderated process. However, recent findings suggest the opposite. We have found that AGA(C8R)-HNG17 confers protection against necrosis in the neuronal cell lines PC-12 and NSC-34, where necrosis is induced in a glucose-free medium by either chemohypoxia or by a shift from apoptosis to necrosis. Our studies in traumatic brain injury models in mice, where necrosis is the main mode of neuronal cell death, have shown that AGA(C8R)-HNG17 has a protective effect. This result is demonstrated by a decrease in a neuronal severity score and by a reduction in brain edema, as measured by magnetic resonance imaging (MRI). An insight into the peptide's antinecrotic mechanism was attained through measurements of cellular ATP levels in PC-12 cells under necrotic conditions, showing that the peptide mitigates a necrosis-associated decrease in ATP levels. Further, we demonstrate the peptide's direct enhancement of the activity of ATP synthase activity, isolated from rat-liver mitochondria, suggesting that AGA(C8R)-HNG17 targets the mitochondria and regulates cellular ATP levels. Thus, AGA(C8R)-HNG17 has potential use for the development of drug therapies for necrosis-related diseases, for example, traumatic brain injury, stroke, myocardial infarction, and other conditions for which no efficient drug-based treatment is currently available. Finally, this study provides new insight into the mechanisms underlying the antinecrotic mode of action of AGA(C8R)-HNG17.

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

Results from this study5

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone5

In this study, Humanin 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 Humanin.

01AnimalNot a test of Humanin aloneAnimal study (in vivo)Efficacy outcome
In mice with traumatic brain injury, AGA(C8R)-HNG17 decreased the neuronal severity score.
In plain wordsIn mice with brain injury, the humanin derivative AGA(C8R)-HNG17 lowered a neuronal severity score.
Peptide
Humanin
Outcome
DecreaseNeuronal severity score after traumatic brain injury
Study
mousen: not reported in source
traumatic brain injury
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
Our studies in traumatic brain injury models in mice, where necrosis is the main mode of neuronal cell death, have shown that AGA(C8R)-HNG17 has a protective effect.
1 context sentence(design, population, supporting numbers)
Summary · context
This result is demonstrated by a decrease in a neuronal severity score and by a reduction in brain edema, as measured by magnetic resonance imaging (MRI).
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-2606201902
02AnimalNot a test of Humanin aloneAnimal study (in vivo)Efficacy outcome
In mice with traumatic brain injury, AGA(C8R)-HNG17 reduced brain edema as measured by MRI.
In plain wordsIn mice with brain injury, the humanin derivative AGA(C8R)-HNG17 reduced brain swelling.
Peptide
Humanin
Outcome
DecreaseBrain edema on MRI after traumatic brain injury
Study
mousen: not reported in source
traumatic brain injury
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
Our studies in traumatic brain injury models in mice, where necrosis is the main mode of neuronal cell death, have shown that AGA(C8R)-HNG17 has a protective effect.
1 context sentence(design, population, supporting numbers)
Summary · context
This result is demonstrated by a decrease in a neuronal severity score and by a reduction in brain edema, as measured by magnetic resonance imaging (MRI).
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-2606201903
03LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
In PC-12 and NSC-34 neuronal cell lines in glucose-free medium, the humanin derivative AGA(C8R)-HNG17 protected against necrosis.
In plain wordsIn cells, the humanin derivative AGA(C8R)-HNG17 protected nerve cells against necrotic cell death.
Peptide
Humanin
Outcome
DecreaseNecrosis induced by chemohypoxia or apoptosis-to-necrosis shift
Study
n: not reported in source
PC-12 and NSC-34 neuronal cell lines
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
We have found that AGA(C8R)-HNG17 confers protection against necrosis in the neuronal cell lines PC-12 and NSC-34, where necrosis is induced in a glucose-free medium by either chemohypoxia or by a shift from apoptosis to necrosis.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-2606201901
04LabNot a test of Humanin aloneIn vitro (cells)Mechanism
In PC-12 cells under necrotic conditions, AGA(C8R)-HNG17 mitigated the necrosis-associated decrease in ATP levels.
In plain wordsIn cells, the humanin derivative AGA(C8R)-HNG17 reduced the drop in cell energy (ATP) seen during necrosis.
Peptide
Humanin
Outcome
IncreaseCellular ATP levels under necrotic conditions
Study
n: not reported in source
PC-12 cells under necrotic conditions
Outcome group
Mitochondrial function · Nervous system and cognition
Source sentences
Summary
An insight into the peptide's antinecrotic mechanism was attained through measurements of cellular ATP levels in PC-12 cells under necrotic conditions, showing that the peptide mitigates a necrosis-associated decrease in ATP levels.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-2606201904
05LabNot a test of Humanin aloneIn vitro (cell-free)Mechanism
AGA(C8R)-HNG17 directly enhanced the activity of ATP synthase isolated from rat-liver mitochondria.
In plain wordsIn lab tests, the humanin derivative AGA(C8R)-HNG17 increased the activity of an energy-making enzyme from rat liver mitochondria.
Peptide
Humanin
Outcome
IncreaseATP synthase activity
Study
ratn: not reported in source
ATP synthase isolated from rat-liver mitochondria
Outcome group
Mitochondrial function · Whole body
Source sentences
Summary
Further, we demonstrate the peptide's direct enhancement of the activity of ATP synthase activity, isolated from rat-liver mitochondria, suggesting that AGA(C8R)-HNG17 targets the mitochondria and regulates cellular ATP levels.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-2606201905

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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