ArticleJournal of Alzheimer's disease : JAD2019
MK0677, a Ghrelin Mimetic, Improves Neurogenesis but Fails to Prevent Hippocampal Lesions in a Mouse Model of Alzheimer's Disease Pathology.
Article in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Integrative role of orexigenic peptides in neuroprotection and neurodegenerative disease modulation.Bioscience reports · 2026Review
- Review
- Traumatic brain injury alters the effects of class II invariant peptide (CLIP) antagonism on chronic meningeal CLIP + B cells, neuropathology, and neurobehavioral impairment in 5xFAD mice.Journal of neuroinflammation · 2024Article
- Approaches for Increasing Cerebral Efflux of Amyloid-β in Experimental Systems.Journal of Alzheimer's disease : JAD · 2024Review
- Elaboration of the Effective Multi-Target Therapeutic Platform for the Treatment of Alzheimer's Disease Based on Novel Monoterpene-Derived Hydroxamic Acids.International journal of molecular sciences · 2023Article
- Liver-expressed antimicrobial peptide 2 elevation contributes to age-associated cognitive decline.JCI insight · 2023Article
- Ghrelin system in Alzheimer's disease.Current opinion in neurobiology · 2023Review
- Mitochondrial Dysfunction Links to Impaired Hippocampal Serotonin Release in a Mouse Model of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Article
- Elevated Ghrelin Promotes Hippocampal Ghrelin Receptor Defects in Humanized Amyloid-β Knockin Mice During Aging.Journal of Alzheimer's disease : JAD · 2023Article
- Advances in the Development of Nonpeptide Small Molecules Targeting Ghrelin Receptor.Journal of medicinal chemistry · 2022Review
- Nonobese Male Patients with Alzheimer's Disease Are Vulnerable to Decrease in Plasma Leptin.Journal of Alzheimer's disease : JAD · 2022Article
- From Menopause to Neurodegeneration-Molecular Basis and Potential Therapy.International journal of molecular sciences · 2021Review
- Article
- Ghrelin-Mediated Regeneration and Plasticity After Nervous System Injury.Frontiers in cell and developmental biology · 2021Review
- Role of sex and high-fat diet in metabolic and hypothalamic disturbances in the 3xTg-AD mouse model of Alzheimer's disease.Journal of neuroinflammation · 2020Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Hippocampal lesions including synaptic injury, neuroinflammation, and impaired neurogenesis are featured pathology closely associated with neuronal stress and cognitive impairment in Alzheimer's disease (AD). Previous studies suggest that ghrelin and its receptor, growth hormone secretagogue receptor 1α (GHSR1α), promote hippocampal synaptic function and neurogenesis. GHSR1α activation thus holds the potential to be a therapeutic avenue for the treatment of hippocampal pathology in AD; however, a comprehensive study on the preventive effect of MK0677 on hippocampal lesions in AD-related conditions is still lacking. In this study, we treated a transgenic mouse model of AD-like amyloidosis (5xFAD mice) at the asymptomatic stage with MK0677, a potent ghrelin mimetic. We found that MK0677 fostered hippocampal neurogenesis in 5xFAD mice but observed little preventive function with regards to the development of hippocampal amyloid-β (Aβ) deposition, synaptic loss, microglial activation, or cognitive impairment. Furthermore, MK0677 at a dose of 3 mg/kg significantly increased 5xFAD mouse mortality. Despite enhanced hippocampal neurogenesis, MK0677 treatment has little beneficial effect to prevent hippocampal lesions or cognitive deficits against Aβ toxicity. This study, together with a failed large-scale clinical trial, suggests the ineffectiveness of MK0677 alone for AD prevention and treatment.
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