Genetic Association between Ghrelin Polymorphisms and Alzheimer’s Disease in a Japanese Population

Shibata, Nobuto; Ohnuma, Tohru; Kuerban, Bolati; Komatsu, Miwa; Arai, Heii

doi:10.1159/000333075

Cited by 22 publications

(14 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several lines of evidence suggest that ghrelin has a critical role in AD pathogenesis and therapy [50,51]. It has been shown that the expression levels of ghrelin and ghrelin receptor were profoundly decreased in the patients with AD [52,53] and the single nucleotide polymorphisms of the ghrelin gene are associated with AD patients [54]. The systemic injection of ghrelin and ghrelin agonist was demonstrated to attenuate the memory impairment in the A␤PP transgenic mouse model of AD [55,56].…”

Section: Discussionmentioning

confidence: 99%

Impaired Hippocampal Neurogenesis and its Enhancement with Ghrelin in 5XFAD Mice

Moon

Mook‐Jung

2014

JAD

102

View full text Add to dashboard Cite

Alzheimer's disease (AD) is an age-related neurological disorder characterized by the deposition of amyloid-β (Aβ), cognitive deficits, and neuronal loss. The decline in neurogenic capacity could participate in neuronal vulnerability and contribute to memory impairment in AD. In our longitudinal study with AD model mice (5XFAD mice), we found that the number of doublecortin (neurogenesis marker)-positive cells in 5XFAD mice was significantly decreased compared to wild-type littermate mice. Using Aβ immunostaining with 4G8 antibody, we observed that impairment in neurogenesis might be associated with the deposits of amyloid plaques. To investigate the effect of the neurogenic hormone ghrelin on defective neurogenesis in the AD brain, 5XFAD mice were administered peripherally with ghrelin. We found that treatment with ghrelin increased the number of doublecortin, HH3, and calretinin-stained cells in the hippocampus of 5XFAD mice. In 5XFAD mice treated with ghrelin, the 4G8-positive area was not significantly different from the saline-treated 5XFAD mice. Together, these findings suggest that hippocampal neurogenesis is impaired in 5XFAD mice and that treatment with ghrelin successfully rescued the abnormality of neurogenesis in 5XFAD mice without affecting Aβ pathology.

show abstract

Section: Discussionmentioning

confidence: 99%

Impaired Hippocampal Neurogenesis and its Enhancement with Ghrelin in 5XFAD Mice

Moon

Mook‐Jung

2014

JAD

102

View full text Add to dashboard Cite

show abstract

“…This study also revealed that the ratio between GHSR1a and GHSR1b receptors was altered in AD patients, suggesting that these changes in the ghrelin system could be involved in the severity of the disease. The fact that recent data indicate that SNPs of the ghrelin gene are associated with the age of AD onset (Shibata et al 2011), together with the observation that male patients with AD have a disruption in the normal compensatory modulation of ghrelin secretion (Theodoropoulou et al 2012), strongly reinforce the idea that the ghrelin system should be considered as a potential therapeutic target in the treatment of AD-related comorbidities.…”

Section: Neurodegenerationmentioning

confidence: 91%

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

Gahete

Rincón-Fernández

Villa-Osaba

et al. 2013

Journal of Endocrinology

View full text Add to dashboard Cite

Ghrelin is a 28-amino acid acylated hormone, highly expressed in the stomach, which binds to its cognate receptor (GHSR1a) to regulate a plethora of relevant biological processes, including food intake, energy balance, hormonal secretions, learning, inflammation, etc. However, ghrelin is, in fact, the most notorious component of a complex, intricate regulatory system comprised of a growing number of alternative peptides (e.g. obestatin, unacylated ghrelin, and In1-ghrelin, etc.), known (GHSRs) and, necessarily unknown receptors, as well as modifying enzymes (e.g. ghrelin-O-acyl-transferase), which interact among them as well as with other regulatory systems in order to tightly modulate key (patho)-physiological processes. This multiplicity of functions and versatility of the ghrelin system arise from a dual, genetic and functional, complexity. Importantly, a growing body of evidence suggests that dysregulation in some of the components of the ghrelin system can lead to or influence the development and/or progression of highly concerning pathologies such as endocrine-related tumors, inflammatory/cardiovascular diseases, and neurodegeneration, wherein these altered components could be used as diagnostic, prognostic, or therapeutic targets. In this context, the aim of this review is to integrate and comprehensively analyze the multiple components and functions of the ghrelin system described to date in order to define and understand its biological and (patho)-physiological significance.

show abstract

“…Although there are no reports on genetic association between ghrelin gene polymorphisms and AD [179], it was later reported that ghrelin gene variants are associated with cognitive dysfunction [180]. However, the exact nature of the relationship between ghrelin and cognitive function in healthy subjects is still unclear, since plasma ghrelin levels have been reported to rather be inversely associated with cognitive function in elderly non-demented patients [181].…”

Section: Neurodegenerative Disordersmentioning

confidence: 99%

Therapeutic Potential of Targeting the Ghrelin Pathway

Colldén

Tschöp

Müller

2017

IJMS

124

View full text Add to dashboard Cite

Ghrelin was discovered in 1999 as the endogenous ligand of the growth-hormone secretagogue receptor 1a (GHSR1a). Since then, ghrelin has been found to exert a plethora of physiological effects that go far beyond its initial characterization as a growth hormone (GH) secretagogue. Among the numerous well-established effects of ghrelin are the stimulation of appetite and lipid accumulation, the modulation of immunity and inflammation, the stimulation of gastric motility, the improvement of cardiac performance, the modulation of stress, anxiety, taste sensation and reward-seeking behavior, as well as the regulation of glucose metabolism and thermogenesis. Due to a variety of beneficial effects on systems’ metabolism, pharmacological targeting of the endogenous ghrelin system is widely considered a valuable approach to treat metabolic complications, such as chronic inflammation, gastroparesis or cancer-associated anorexia and cachexia. The aim of this review is to discuss and highlight the broad pharmacological potential of ghrelin pathway modulation for the treatment of anorexia, cachexia, sarcopenia, cardiopathy, neurodegenerative disorders, renal and pulmonary disease, gastrointestinal (GI) disorders, inflammatory disorders and metabolic syndrome.

show abstract

Genetic Association between Ghrelin Polymorphisms and Alzheimer’s Disease in a Japanese Population

Cited by 22 publications

References 38 publications

Impaired Hippocampal Neurogenesis and its Enhancement with Ghrelin in 5XFAD Mice

Impaired Hippocampal Neurogenesis and its Enhancement with Ghrelin in 5XFAD Mice

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

Therapeutic Potential of Targeting the Ghrelin Pathway

Contact Info

Product

Resources

About