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Study · Animal study (in vivo) · mouse · 2018

5 results

MK-0677, a Ghrelin Agonist, Alleviates Amyloid Beta-Related Pathology in 5XFAD Mice, an Animal Model of Alzheimer's Disease.

Jeong YO, Shin SJ, Park JY, Ku BK, Song JS, Kim JJ, Jeon SG, Lee SM, Moon M

International journal of molecular sciences18 Jun 2018Cited by 41 (Europe PMC)

PMID29912176 (opens in a new tab)PMCIDPMC6032329 (opens in a new tab)DOI10.3390/ijms19061800 (opens in a new tab)PepBankPUB-29912176
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Summary

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, neuroinflammation, and neuronal death. The primary pathogenic cause is believed to be the accumulation of pathogenic amyloid beta (Aβ) assemblies in the brain. Ghrelin, which is a peptide hormone predominantly secreted from the stomach, is an endogenous ligand for the growth hormone secretagogue-receptor type 1a (GHS-R1a). MK-0677 is a ghrelin agonist that potently stimulates the GHS-R1a ghrelin receptor. Interestingly, previous studies have shown that ghrelin improves cognitive impairments and attenuates neuronal death and neuroinflammation in several neurological disorders. However, it is unknown whether MK-0677 can affect Aβ accumulation or Aβ-mediated pathology in the brains of patients with AD. Therefore, we examined the effects of MK-0677 administration on AD-related pathology in 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD. MK-0677 was intraperitoneally administered to three-month-old 5XFAD mice. To visualize Aβ accumulation, neuroinflammation, and neurodegeneration, thioflavin-S staining and immunostaining with antibodies against Aβ (4G8), ionized calcium-binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), neuronal nuclear antigen (NeuN), and synaptophysin were conducted in the neocortex of 5XFAD and wild-type mice, and to evaluate changes of phosphorylated cyclic adenosine monophosphate (cAMP) response element binding protein (pCREB) levels, immunostaining with antibody against pCREB was performed in dentate gyrus of the hippocampus of 5XFAD and wild-type mice. The histological analyses indicated that MK-0677-treated 5XFAD mice showed reduced Aβ deposition, gliosis, and neuronal and synaptic loss in the deep cortical layers, and inhibited the decrement of pCREB levels in dentate gyrus of the hippocampus compared to vehicle-treated 5XFAD mice. Our results showed that activation of the ghrelin receptor with MK-0677 inhibited the Aβ burden, neuroinflammation, and neurodegeneration, which suggested that MK-0677 might have potential as a treatment of the early phase of AD.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In 5XFAD mice, MK-0677 reduced Aβ deposition in deep cortical layers versus vehicle.

    In plain wordsIn mice with an Alzheimer's disease model, MK-0677 reduced cortical amyloid deposits compared with vehicle.

    Peptide
    MK-677 (ibutamoren)
    Outcome
    DecreaseAβ deposition
    Study

    mousen: not reported in source

    5XFAD mice
    Comparator
    Vehicle-treated 5XFAD mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    The histological analyses indicated that MK-0677-treated 5XFAD mice showed reduced Aβ deposition, gliosis, and neuronal and synaptic loss in the deep cortical layers, and inhibited the decrement of pCREB levels in dentate gyrus of the hippocampus compared to vehicle-treated 5XFAD mice.
    2 context sentences
    Summary · context
    Therefore, we examined the effects of MK-0677 administration on AD-related pathology in 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD.
    Summary · context
    MK-0677 was intraperitoneally administered to three-month-old 5XFAD mice.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In 5XFAD mice, MK-0677 reduced gliosis in deep cortical layers versus vehicle.

    In plain wordsIn mice with an Alzheimer's disease model, MK-0677 reduced cortical gliosis compared with vehicle.

    Peptide
    MK-677 (ibutamoren)
    Outcome
    DecreaseGliosis
    Study

    mousen: not reported in source

    5XFAD mice
    Comparator
    Vehicle-treated 5XFAD mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    The histological analyses indicated that MK-0677-treated 5XFAD mice showed reduced Aβ deposition, gliosis, and neuronal and synaptic loss in the deep cortical layers, and inhibited the decrement of pCREB levels in dentate gyrus of the hippocampus compared to vehicle-treated 5XFAD mice.
    2 context sentences
    Summary · context
    Therefore, we examined the effects of MK-0677 administration on AD-related pathology in 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD.
    Summary · context
    MK-0677 was intraperitoneally administered to three-month-old 5XFAD mice.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In 5XFAD mice, MK-0677 reduced neuronal loss in deep cortical layers versus vehicle.

    In plain wordsIn mice with an Alzheimer's disease model, MK-0677 reduced cortical neuron loss compared with vehicle.

    Peptide
    MK-677 (ibutamoren)
    Outcome
    DecreaseNeuronal loss
    Study

    mousen: not reported in source

    5XFAD mice
    Comparator
    Vehicle-treated 5XFAD mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    The histological analyses indicated that MK-0677-treated 5XFAD mice showed reduced Aβ deposition, gliosis, and neuronal and synaptic loss in the deep cortical layers, and inhibited the decrement of pCREB levels in dentate gyrus of the hippocampus compared to vehicle-treated 5XFAD mice.
    2 context sentences
    Summary · context
    Therefore, we examined the effects of MK-0677 administration on AD-related pathology in 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD.
    Summary · context
    MK-0677 was intraperitoneally administered to three-month-old 5XFAD mice.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In 5XFAD mice, MK-0677 reduced synaptic loss in deep cortical layers versus vehicle.

    In plain wordsIn mice with an Alzheimer's disease model, MK-0677 reduced cortical synaptic loss compared with vehicle.

    Peptide
    MK-677 (ibutamoren)
    Outcome
    DecreaseSynaptic loss
    Study

    mousen: not reported in source

    5XFAD mice
    Comparator
    Vehicle-treated 5XFAD mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    The histological analyses indicated that MK-0677-treated 5XFAD mice showed reduced Aβ deposition, gliosis, and neuronal and synaptic loss in the deep cortical layers, and inhibited the decrement of pCREB levels in dentate gyrus of the hippocampus compared to vehicle-treated 5XFAD mice.
    2 context sentences
    Summary · context
    Therefore, we examined the effects of MK-0677 administration on AD-related pathology in 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD.
    Summary · context
    MK-0677 was intraperitoneally administered to three-month-old 5XFAD mice.
  5. 05AnimalAnimal study (in vivo)Mechanism

    In 5XFAD mice, MK-0677 inhibited the hippocampal dentate gyrus pCREB decrease versus vehicle.

    In plain wordsIn mice with an Alzheimer's disease model, MK-0677 preserved hippocampal pCREB levels compared with vehicle.

    Peptide
    MK-677 (ibutamoren)
    Outcome
    IncreasepCREB levels
    Study

    mousen: not reported in source

    5XFAD mice
    Comparator
    Vehicle-treated 5XFAD mice
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated · intraperitonealAs given in this study (mouse).

    Source sentences

    Summary
    The histological analyses indicated that MK-0677-treated 5XFAD mice showed reduced Aβ deposition, gliosis, and neuronal and synaptic loss in the deep cortical layers, and inhibited the decrement of pCREB levels in dentate gyrus of the hippocampus compared to vehicle-treated 5XFAD mice.
    2 context sentences
    Summary · context
    Therefore, we examined the effects of MK-0677 administration on AD-related pathology in 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD.
    Summary · context
    MK-0677 was intraperitoneally administered to three-month-old 5XFAD mice.

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.

  1. Version 2Current

    14 Oct 2026, 05:02 UTC

    Study results updated

  2. Version 1

    14 Oct 2026, 01:46 UTC

    First added · source update from Europe PMC

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Terms as the source lists them.

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