Ghrelin in Alzheimer’s disease: Pathologic roles and therapeutic implications

Jeon, Seong Gak; Hong, Sang Bum; Nam, Yunkwon; Tae, Jungyeon; Yoo, Anji; Song, Eun Ji; Kim, Kun Il; Lee, Dongje; Park, Junyong; Lee, Sang Min; Kim, Jin-il; Moon, Minho

doi:10.1016/j.arr.2019.100945

Cited by 42 publications

(33 citation statements)

References 202 publications

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“…Ghrelin has not only been reported to regulate fat metabolism but also presented abilities to stimulate downstream pathways and affect cognitive functions 249 . It participates in many AD pathology, including Aβ homeostasis, mitochondrial deficit, neuroinflammation, and hyperphosphorylation of tau, and so forth 250 . Actually, the administration of ghrelin, also including ghrelin receptor agonists and ghrelin mimetics, showed encouraging attenuative effects on AD 251,252 .…”

Section: Discussion and Perspectivementioning

confidence: 99%

Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism

Xing

Xiong

et al. 2020

Medicinal Research Reviews

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Structural information of butyrylcholinesterase (BChE) and its variants associated with several diseases are discussed here. Pure human BChE has been proved safe and effective in treating organophosphorus (OPs) poisoning and has completed Phase 1 and 2 pharmacokinetic (PK) and safety studies. The introduction of specific mutations into native BChE to endow it a self‐reactivating property has gained much progress in producing effective OPs hydrolases. The hydrolysis ability of native BChE on cocaine has been confirmed but was blocked to clinical application due to poor PK properties. Several BChE mutants with elevated cocaine hydrolysis activity were published, some of which have shown safety and efficiency in treating cocaine addiction of human. The increased level of BChE in progressed Alzheimer's disease patients made it a promising target to elevate acetylcholine level and attenuate cognitive status. A variety of selective BChE inhibitors with high inhibitory activity published in recent years are reviewed here. BChE could influence the weight and insulin secretion and resistance of BChE knockout (KO) mice through hydrolyzing ghrelin. The BChE‐ghrelin pathway could also regulate aggressive behaviors of BChE‐KO mice.

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Section: Discussion and Perspectivementioning

confidence: 99%

Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism

Xing

Xiong

et al. 2020

Medicinal Research Reviews

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“…Activation of GHSR was shown to modulate JAK2-associated PI3K and AKT phosphorylation as well as MAPK signaling (33)(34)(35)(36). Moreover, AKT signaling induces Ser9 phosphorylation of GSK3β, which is involved in the regulation of DEL1 transcription (20).…”

Section: Erm Upregulates Del-1 Mrna and Protein Levels In Vitro And Imentioning

confidence: 99%

Erythromycin inhibits neutrophilic inflammation and mucosal disease by upregulating DEL-1

Maekawa¹,

Tamura²,

Domon³

et al. 2020

JCI Insight

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“…Studies have been shown that administration of ghrelin decreased REM sleep and increased slow wave sleep in elderly men (Kluge et al, 2010) and promoted non-REM sleep in male mice (Obal et al, 2003). Several studies have been reported that GHS-R1 mRNA is highly expressed in the SCN (Zigman et al, 2006) and ARC (Jeon et al, 2019). It is well known that neurons in the SCN are projected to the dorsal parvocellular paraventricular nucleus (PVHd), and neurons in the PVHd are projected to sympathetic preganglionic neurons, which in turn regulate melatonin secretion by the pineal gland (Saper et al, 2005).…”

Section: The Role Of Ghrelin In Ad-related Sleep-wake Disturbancesmentioning

confidence: 99%

“…Remarkably, extensive evidence has indicated that ghrelin may alleviate AD-related pathology such as Aβ accumulation ( Dhurandhar et al, 2013 ; Jeong et al, 2018 ), tau hyperphosphorylation ( Kang et al, 2015 ), mitochondrial dysfunction ( Chung et al, 2007 ), impaired adult neurogenesis ( Moon et al, 2014 ), and neuroinflammation ( Moon et al, 2011 ; Sibilia et al, 2012 ). Therefore, due to its potential for mitigating AD-related pathologies, ghrelin could be a possible therapeutic target for AD ( Jeon et al, 2019 ). In addition, several studies have reported that ghrelin plays a protective role in metabolic syndrome ( Broglio et al, 2004 ) and various psychiatric disorders, including depression ( Carlini et al, 2012 ), sleep–wake disturbances ( Yannielli et al, 2007 ), and abnormal eating behaviors ( Overduin et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

The Potential Roles of Ghrelin in Metabolic Syndrome and Secondary Symptoms of Alzheimer’s Disease

Kim¹,

Nam²,

Shin³

et al. 2020

Front. Neurosci.

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Although the major causative factors of Alzheimer's disease (AD) are the accumulation of amyloid β and hyperphosphorylated tau, AD can also be caused by metabolic dysfunction. The major clinical symptom of AD is cognitive dysfunction. However, AD is also accompanied by various secondary symptoms such as depression, sleep-wake disturbances, and abnormal eating behaviors. Interestingly, the orexigenic hormone ghrelin has been suggested to have beneficial effects on AD-related metabolic syndrome and secondary symptoms. Ghrelin improves lipid distribution and alters insulin sensitivity, effects that are hypothesized to delay the progression of AD. Furthermore, ghrelin can relieve depression by enhancing the secretion of hormones such as serotonin, noradrenaline, and orexin. Moreover, ghrelin can upregulate the expression of neurotrophic factors such as brain-derived neurotrophic factor and modulate the release of proinflammatory cytokines such as tumor necrosis factor α and interleukin 1β. Ghrelin alleviates sleep-wake disturbances by increasing the levels of melatonin, melanin-concentrating hormone. Ghrelin reduces the risk of abnormal eating behaviors by increasing neuropeptide Y and γ-aminobutyric acid. In addition, ghrelin increases food intake by inhibiting fatty acid biosynthesis. However, despite the numerous studies on the role of ghrelin in the AD-related pathology and metabolic disorders, there are only a few studies that investigate the effects of ghrelin on secondary symptoms associated with AD. In this mini review, our purpose is to provide the insights of future study by organizing the previous studies for the role of ghrelin in AD-related pathology and metabolic disorders.

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Ghrelin in Alzheimer’s disease: Pathologic roles and therapeutic implications

Cited by 42 publications

References 202 publications

Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism

Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism

Erythromycin inhibits neutrophilic inflammation and mucosal disease by upregulating DEL-1

The Potential Roles of Ghrelin in Metabolic Syndrome and Secondary Symptoms of Alzheimer’s Disease

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