Intranasal delivery of mitochondrial protein humanin rescues cell death and promotes mitochondrial function in Parkinson's disease.

Kim KH

Theranostics29 May 2023Cited by 26 (Europe PMC)

PMID37351170PMCIDPMC10283052DOI10.7150/thno.84165PepBankPUB-37351170

Summary

Rationale: Mitochondrial dysfunction is a key factor in the pathogenesis of Parkinson's disease (PD). Accordingly, many aspects of mitochondrial function have been studied as a putative therapeutic target. Here we present a novel strategy to promote mitochondrial function and protect against Parkinson's disease by the peptide encoded within mitochondrial genome, mitochondria-derived peptide (MDP) humanin (HN). Methods: To test humanin as a potential biomarker in PD, we measured protein levels of circulating humanin from the plasma of PD patients and transgenic or neurotoxic mouse models of PD. Next, we aimed to identify whether HN peptide treatment can regulate its activity or expression. Using mouse models of PD, we assessed HN delivery to the brain via the nasal route of administration. We further revealed a possible mechanism underlying the therapeutic effectiveness of HN peptide for PD using in vitro and ex vivo model of PD. Results: Although the expression of intracellular HN was not correlated with PD, HN treatment itself could induce intracellular HN expression and enhance mitochondrial biogenesis inducing mitochondrial gene expression. After intranasal administration, HN peptide resulted in neuroprotection and behavioral recovery in an animal model of PD. Interestingly, HN peptide following intranasal delivery was found within the brain, mainly via the trigeminal pathways. Mechanistically, HN treatment induced activation of phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway which led to enhanced mitochondrial biogenesis resulting in upregulation of mitochondrial gene including humanin. Conclusion: These data support a novel role of mitochondrial protein humanin in mitochondrial function and neuronal survival against Parkinson's disease, in which humanin treatment is sufficient for stimulating mitochondrial gene expression.

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

Results from this study8

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

01AnimalAnimal study (in vivo)Efficacy outcome
In a mouse model of Parkinson's disease, intranasal humanin peptide resulted in neuroprotection.
In plain wordsIn mice with a Parkinson's model, humanin given through the nose protected nerve cells.
Peptide
Humanin
Outcome
IncreaseNeuroprotection
Study
mousen: not reported in source
Mouse model of Parkinson's disease
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated · intranasalAs given in this study (mouse).
Source sentences
Summary
After intranasal administration, HN peptide resulted in neuroprotection and behavioral recovery in an animal model of PD.
1 context sentence(design, population, supporting numbers)
Summary · context
Using mouse models of PD, we assessed HN delivery to the brain via the nasal route of administration.
Show in the study text Report a problemFND-3735117006
02AnimalAnimal study (in vivo)Efficacy outcome
In a mouse model of Parkinson's disease, intranasal humanin peptide resulted in behavioral recovery.
In plain wordsIn mice with a Parkinson's model, humanin given through the nose improved behavior.
Peptide
Humanin
Outcome
IncreaseBehavioral recovery
Study
mousen: not reported in source
Mouse model of Parkinson's disease
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated · intranasalAs given in this study (mouse).
Source sentences
Summary
After intranasal administration, HN peptide resulted in neuroprotection and behavioral recovery in an animal model of PD.
1 context sentence(design, population, supporting numbers)
Summary · context
Using mouse models of PD, we assessed HN delivery to the brain via the nasal route of administration.
Show in the study text Report a problemFND-3735117007
03AnimalAnimal study (in vivo)Pharmacokinetics
After intranasal delivery in mice, humanin peptide was found within the brain, mainly via the trigeminal pathways.
In plain wordsIn mice, humanin given through the nose reached the brain, mainly along the trigeminal nerve routes.
Peptide
Humanin
Outcome
Not applicableBrain delivery after intranasal administration
Study
mousen: not reported in source
Mouse model of Parkinson's disease
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated · intranasalAs given in this study (mouse).
Source sentences
Summary
Interestingly, HN peptide following intranasal delivery was found within the brain, mainly via the trigeminal pathways.
1 context sentence(design, population, supporting numbers)
Summary · context
Using mouse models of PD, we assessed HN delivery to the brain via the nasal route of administration.
Show in the study text Report a problemFND-3735117008
04LabIn vitro (cells)Mechanism
Humanin treatment induced intracellular humanin expression in models of Parkinson's disease.
In plain wordsIn lab tests, humanin treatment raised humanin levels inside cells.
Peptide
Humanin
Outcome
IncreaseIntracellular humanin expression
Study
n: not reported in source
In vitro and ex vivo models of Parkinson's disease
Outcome group
Mitochondrial function · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
HN treatment itself could induce intracellular HN expression and enhance mitochondrial biogenesis inducing mitochondrial gene expression.
1 context sentence(design, population, supporting numbers)
Summary · context
We further revealed a possible mechanism underlying the therapeutic effectiveness of HN peptide for PD using in vitro and ex vivo model of PD.
Show in the study text Report a problemFND-3735117002
05LabIn vitro (cells)Mechanism
Humanin treatment enhanced mitochondrial biogenesis in models of Parkinson's disease.
In plain wordsIn lab tests, humanin treatment boosted the making of new mitochondria.
Peptide
Humanin
Outcome
IncreaseMitochondrial biogenesis
Study
n: not reported in source
In vitro and ex vivo models of Parkinson's disease
Outcome group
Mitochondrial function · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
enhance mitochondrial biogenesis inducing mitochondrial gene expression.
1 context sentence(design, population, supporting numbers)
Summary · context
We further revealed a possible mechanism underlying the therapeutic effectiveness of HN peptide for PD using in vitro and ex vivo model of PD.
Show in the study text Report a problemFND-3735117003
06LabIn vitro (cells)Mechanism
Humanin treatment induced mitochondrial gene expression in models of Parkinson's disease.
In plain wordsIn lab tests, humanin treatment raised mitochondrial gene activity.
Peptide
Humanin
Outcome
IncreaseMitochondrial gene expression
Study
n: not reported in source
In vitro and ex vivo models of Parkinson's disease
Outcome group
Mitochondrial function · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
enhance mitochondrial biogenesis inducing mitochondrial gene expression.
1 context sentence(design, population, supporting numbers)
Summary · context
We further revealed a possible mechanism underlying the therapeutic effectiveness of HN peptide for PD using in vitro and ex vivo model of PD.
Show in the study text Report a problemFND-3735117004
07LabIn vitro (cells)Mechanism
Humanin treatment activated the PI3K/AKT signaling pathway, which led to enhanced mitochondrial biogenesis.
In plain wordsIn lab tests, humanin treatment switched on the PI3K/AKT pathway.
Peptide
Humanin
Outcome
IncreasePI3K/AKT signaling activation
Study
n: not reported in source
In vitro and ex vivo models of Parkinson's disease
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Mechanistically, HN treatment induced activation of phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway which led to enhanced mitochondrial biogenesis resulting in upregulation of mitochondrial gene including humanin.
1 context sentence(design, population, supporting numbers)
Summary · context
We further revealed a possible mechanism underlying the therapeutic effectiveness of HN peptide for PD using in vitro and ex vivo model of PD.
Show in the study text Report a problemFND-3735117005

Natural levels measured1

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

08AnimalEndogenous levelAnimal study (in vivo)Other
Intracellular humanin expression was not correlated with Parkinson's disease.
In plain wordsThe body's own humanin inside cells was not linked to Parkinson's disease in this study.
Peptide
Humanin
Outcome
No significant changeIntracellular humanin expression and PD
Study
mousen: not reported in source
Parkinson's disease models
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
Although the expression of intracellular HN was not correlated with PD
1 context sentence(design, population, supporting numbers)
Summary · context
To test humanin as a potential biomarker in PD, we measured protein levels of circulating humanin from the plasma of PD patients and transgenic or neurotoxic mouse models of PD.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3735117001

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

Subjects

Terms as the source lists them.

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