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Study · Animal study (in vivo) · mouse · 2021

7 results

Melanocortin receptor activation alleviates amyloid pathology and glial reactivity in an Alzheimer's disease transgenic mouse model.

Lau JKY, Tian M, Shen Y, Lau SF, Fu WY, Fu AKY, Ip NY

Scientific reports23 Feb 2021Cited by 16 (Europe PMC)

PMID33623128 (opens in a new tab)PMCIDPMC7902646 (opens in a new tab)DOI10.1038/s41598-021-83932-4 (opens in a new tab)PepBankPUB-33623128
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Summary

Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no disease-modifying treatment. AD progression is characterized by cognitive decline, neuroinflammation, and accumulation of amyloid-beta (Aβ) and neurofibrillary tangles in the brain, leading to neuronal and glial dysfunctions. Neuropeptides govern diverse pathophysiological processes and represent key players in AD pathogenesis, regulating synaptic plasticity, glial cell functions and amyloid pathology. Activation of the pro-opiomelanocortin (POMC)-derived neuropeptide and its receptor from the melanocortin receptor (MCR) family have previously been shown to rescue the impairment in hippocampus-dependent synaptic plasticity in the APP/PS1 mouse model of AD. However, the functional roles of MCR signaling in AD conditions, particularly in glial functions, are largely unknown. In this study, we investigated the potential benefits of MCR activation in AD. In APP/PS1 transgenic mice, we demonstrate that MCR activation mediated by the central administration of its agonist D-Tyr MTII substantially reduces Aβ accumulation, while alleviating global inflammation and astrocytic activation, particularly in the hippocampus. MCR activation prominently reduces the A1 subtype of reactive astrocytes, which is considered a key source of astrocytic neurotoxicity in AD. Concordantly, MCR activation suppresses microglial activation, while enhancing their association with amyloid plaques. The blunted activation of microglia may contribute to the reduction in the neurotoxic phenotypes of astrocytes. Importantly, transcriptome analysis reveals that MCR activation restores the impaired homeostatic processes and microglial reactivity in the hippocampus in APP/PS1 mice. Collectively, our findings demonstrate the potential of MCR signaling as therapeutic target for AD.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In APP/PS1 mice, central administration of the melanocortin agonist D-Tyr MTII substantially reduced amyloid-beta accumulation.

    In plain wordsIn mice with Alzheimer-like disease, the melanocortin agonist D-Tyr MTII, given into the brain, lowered amyloid-beta build-up.

    Peptide
    Melanotan II
    Outcome
    DecreaseAmyloid-beta accumulation
    Study

    mousen: not reported in source

    APP/PS1 transgenic mouse model of Alzheimer's disease
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · central administrationAs given in this study (mouse).

    Source sentences

    Summary
    MCR activation mediated by the central administration of its agonist D-Tyr MTII substantially reduces Aβ accumulation
    1 context sentence
    Summary · context
    In APP/PS1 transgenic mice, we demonstrate that MCR activation mediated by the central administration of its agonist D-Tyr MTII substantially reduces Aβ accumulation, while alleviating global inflammation and astrocytic activation, particularly in the hippocampus.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In APP/PS1 mice, D-Tyr MTII alleviated global inflammation, particularly in the hippocampus.

    In plain wordsIn mice with Alzheimer-like disease, the melanocortin agonist D-Tyr MTII lowered brain inflammation, mostly in the hippocampus.

    Peptide
    Melanotan II
    Outcome
    DecreaseGlobal inflammation
    Study

    mousen: not reported in source

    APP/PS1 transgenic mouse model of Alzheimer's disease
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    Dose not stated · central administrationAs given in this study (mouse).

    Source sentences

    Summary
    MCR activation mediated by the central administration of its agonist D-Tyr MTII substantially reduces Aβ accumulation, while alleviating global inflammation and astrocytic activation, particularly in the hippocampus
    1 context sentence
    Summary · context
    In APP/PS1 transgenic mice, we demonstrate that MCR activation mediated by the central administration of its agonist D-Tyr MTII substantially reduces Aβ accumulation, while alleviating global inflammation and astrocytic activation, particularly in the hippocampus.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In APP/PS1 mice, D-Tyr MTII alleviated astrocytic activation, particularly in the hippocampus.

    In plain wordsIn mice with Alzheimer-like disease, the melanocortin agonist D-Tyr MTII reduced activation of astrocytes, mostly in the hippocampus.

    Peptide
    Melanotan II
    Outcome
    DecreaseAstrocytic activation
    Study

    mousen: not reported in source

    APP/PS1 transgenic mouse model of Alzheimer's disease
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    Dose not stated · central administrationAs given in this study (mouse).

    Source sentences

    Summary
    MCR activation mediated by the central administration of its agonist D-Tyr MTII substantially reduces Aβ accumulation, while alleviating global inflammation and astrocytic activation, particularly in the hippocampus
    1 context sentence
    Summary · context
    In APP/PS1 transgenic mice, we demonstrate that MCR activation mediated by the central administration of its agonist D-Tyr MTII substantially reduces Aβ accumulation, while alleviating global inflammation and astrocytic activation, particularly in the hippocampus.
  4. 04AnimalAnimal study (in vivo)Mechanism

    In APP/PS1 mice, melanocortin receptor activation reduced the A1 subtype of reactive astrocytes.

    In plain wordsIn mice with Alzheimer-like disease, melanocortin receptor activation lowered a harmful type of reactive astrocytes.

    Peptide
    Melanotan II
    Outcome
    DecreaseA1 reactive astrocytes
    Study

    mousen: not reported in source

    APP/PS1 transgenic mouse model of Alzheimer's disease
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    Dose not stated · central administrationAs given in this study (mouse).

    Source sentences

    Summary
    MCR activation prominently reduces the A1 subtype of reactive astrocytes, which is considered a key source of astrocytic neurotoxicity in AD.
    1 context sentence
    Summary · context
    In APP/PS1 transgenic mice, we demonstrate that MCR activation mediated by the central administration of its agonist D-Tyr MTII substantially reduces Aβ accumulation, while alleviating global inflammation and astrocytic activation, particularly in the hippocampus.
  5. 05AnimalAnimal study (in vivo)Mechanism

    In APP/PS1 mice, melanocortin receptor activation suppressed microglial activation.

    In plain wordsIn mice with Alzheimer-like disease, melanocortin receptor activation reduced activation of microglia, the brain's immune cells.

    Peptide
    Melanotan II
    Outcome
    DecreaseMicroglial activation
    Study

    mousen: not reported in source

    APP/PS1 transgenic mouse model of Alzheimer's disease
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    Dose not stated · central administrationAs given in this study (mouse).

    Source sentences

    Summary
    Concordantly, MCR activation suppresses microglial activation
    1 context sentence
    Summary · context
    In APP/PS1 transgenic mice, we demonstrate that MCR activation mediated by the central administration of its agonist D-Tyr MTII substantially reduces Aβ accumulation, while alleviating global inflammation and astrocytic activation, particularly in the hippocampus.
  6. 06AnimalAnimal study (in vivo)Mechanism

    In APP/PS1 mice, melanocortin receptor activation enhanced the association of microglia with amyloid plaques.

    In plain wordsIn mice with Alzheimer-like disease, melanocortin receptor activation brought microglia closer to amyloid plaques.

    Peptide
    Melanotan II
    Outcome
    IncreaseMicroglial association with amyloid plaques
    Study

    mousen: not reported in source

    APP/PS1 transgenic mouse model of Alzheimer's disease
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · central administrationAs given in this study (mouse).

    Source sentences

    Summary
    Concordantly, MCR activation suppresses microglial activation, while enhancing their association with amyloid plaques.
    1 context sentence
    Summary · context
    In APP/PS1 transgenic mice, we demonstrate that MCR activation mediated by the central administration of its agonist D-Tyr MTII substantially reduces Aβ accumulation, while alleviating global inflammation and astrocytic activation, particularly in the hippocampus.
  7. 07AnimalAnimal study (in vivo)Mechanism

    In APP/PS1 mice, transcriptome analysis showed that melanocortin receptor activation restored impaired homeostatic processes and microglial reactivity in the hippocampus.

    In plain wordsIn mice with Alzheimer-like disease, melanocortin receptor activation restored impaired gene activity linked to normal brain function in the hippocampus.

    Peptide
    Melanotan II
    Outcome
    IncreaseHippocampal homeostatic processes and microglial reactivity (transcriptome)
    Study

    mousen: not reported in source

    APP/PS1 transgenic mouse model of Alzheimer's disease
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · central administrationAs given in this study (mouse).

    Source sentences

    Summary
    Importantly, transcriptome analysis reveals that MCR activation restores the impaired homeostatic processes and microglial reactivity in the hippocampus in APP/PS1 mice.
    1 context sentence
    Summary · context
    In APP/PS1 transgenic mice, we demonstrate that MCR activation mediated by the central administration of its agonist D-Tyr MTII substantially reduces Aβ accumulation, while alleviating global inflammation and astrocytic activation, particularly in the hippocampus.

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

    10 Oct 2026, 09:43 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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