Ghrelin Receptor Signaling: A Promising Therapeutic Target for Metabolic Syndrome and Cognitive Dysfunction

被引：45

作者：

Cong, Wei-na ^{[1
]}

Golden, Erin ^{[2
]}

Pantaleo, Nick ^{[3
]}

White, Caitlin M. ^{[1
]}

Maudsley, Stuart ^{[3
]}

Martin, Bronwen ^{[1
]}

机构：

[1] NIA, Metab Unit, Clin Invest Lab, Baltimore, MD 21224 USA

[2] Johns Hopkins Sch Med, Baltimore, MD 21287 USA

[3] NIA, Receptor Pharmacol Unit, Neurosci Lab, Baltimore, MD 21224 USA

来源：

CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS | 2010年 / 9卷 / 05期

关键词：

Cognitive function; energy balance; ghrelin; growth hormone secretagagogue receptor; memory; metabolic disorders; neuroprotection; obesity; HORMONE SECRETAGOGUE RECEPTOR; CELL-DEATH; FOOD-INTAKE; DOPAMINERGIC-NEURONS; CIRCULATING GHRELIN; PANCREATIC-ISLETS; ACYLATED PEPTIDE; INSULIN-RELEASE; OBESITY; EXPRESSION;

D O I：

10.2174/187152710793361513

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

The neuroendocrine hormone ghrelin is an octanoylated 28-residue peptide that exerts numerous physiological functions. Ghrelin exerts its effects on the body mainly through a highly conserved G protein-coupled receptor known as the growth hormone secretagagogue receptor subtype 1a (GHS-R1a). Ghrelin and GSH-R1a are widely expressed in both peripheral and central tissues/organs, and ghrelin signaling plays a critical role in maintaining energy balance and neuronal health. The multiple orexigenic effects of ghrelin and its receptor have been studied in great detail, and GHS-R1a-mediated ghrelin signaling has long been a promising target for the treatment of metabolic disorders, such as obesity. In addition to its well-characterized metabolic effects, there is also mounting evidence that ghrelin-mediated GHS-R1a signaling exerts neuroprotective effects on the brain. In this review, we will summarize some of the effects of ghrelin-mediated GSH-R1a signaling on peripheral energy balance and cognitive function. We will also discuss the potential pharmacotherapeutic role of GSH-R1a-mediated ghrelin signaling for the treatment of complex neuroendocrine disorders.

引用

页码：557 / 563

页数：7

共 80 条

[1]

Obesity and eating disorders [J].

Allison, KC ;

Stunkard, AJ .

PSYCHIATRIC CLINICS OF NORTH AMERICA, 2005, 28 (01) :55-+

[2]

Ghrelin Promotes and Protects Nigrostriatal Dopamine Function via a UCP2-Dependent Mitochondrial Mechanism [J].

Andrews, Zane B. ;

Erion, Derek ;

Beiler, Rudolph ;

Liu, Zhong-Wu ;

Abizaid, Alfonso ;

Zigman, Jeffrey ;

Elsworth, John D. ;

Savitt, Joseph M. ;

DiMarchi, Richard ;

Tschoep, Matthias ;

Roth, Robert H. ;

Gao, Xiao-Bing ;

Horvath, Tamas L. .

JOURNAL OF NEUROSCIENCE, 2009, 29 (45) :14057-14065

[3]

Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans [J].

Ariyasu, H ;

Takaya, K ;

Tagami, T ;

Ogawa, Y ;

Hosoda, K ;

Akamizu, T ;

Suda, M ;

Koh, T ;

Natsui, K ;

Toyooka, S ;

Shirakami, G ;

Usui, T ;

Shimatsu, A ;

Doi, K ;

Hosoda, H ;

Kojima, M ;

Kangawa, K ;

Nakao, K .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (10) :4753-4758

[4]

Cognitive enhancing effects of ghrelin receptor agonists [J].

Atcha, Zeenat ;

Chen, Woei-Shin ;

Ong, Agnes B. ;

Wong, Fong-Kuan ;

Neo, Aveline ;

Browne, Edward R. ;

Witherington, Jason ;

Pemberton, Darrel J. .

PSYCHOPHARMACOLOGY, 2009, 206 (03) :415-427

[5]

Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT [J].

Baldanzi, G ;

Filigheddu, N ;

Cutrupi, S ;

Catapano, F ;

Bonissoni, S ;

Fubini, A ;

Malan, D ;

Baj, G ;

Granata, R ;

Broglio, F ;

Papotti, M ;

Surico, N ;

Bussolino, F ;

Isgaard, J ;

Deghenghi, R ;

Sinigaglia, F ;

Prat, M ;

Muccioli, G ;

Ghigo, E ;

Graziani, A .

JOURNAL OF CELL BIOLOGY, 2002, 159 (06) :1029-1037

[6]

Neurodegenerative diseases and oxidative stress [J].

Barnham, KJ ;

Masters, CL ;

Bush, AI .

NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (03) :205-214

[7]

Cell death in the nervous system [J].

Bredesen, Dale E. ;

Rao, Rammohan V. ;

Mehlen, Patrick .

NATURE, 2006, 443 (7113) :796-802

[8]

Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans [J].

Broglio, F ;

Arvat, E ;

Benso, A ;

Gottero, C ;

Muccioli, G ;

Papotti, M ;

van der Lely, AJ ;

Deghenghi, R ;

Ghigo, E .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (10) :5083-5086

[9]

Expression of ghrelin in the cyclic and pregnant rat ovary [J].

Caminos, JE ;

Tena-Sempere, M ;

Gaytán, F ;

Sanchez-Criado, JE ;

Barreiro, ML ;

Nogueiras, R ;

Casanueva, FF ;

Aguilar, E ;

Diéguez, C .

ENDOCRINOLOGY, 2003, 144 (04) :1594-1602

[10]

Ghrelin increases anxiety-like behavior and memory retention in rats [J].

Carlini, VP ;

Monzón, ME ;

Varas, MM ;

Cragnolini, AB ;

Schiöth, HB ;

Scimonelli, TN ;

de Barioglio, SR .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 299 (05) :739-743

← 1 2 3 4 5 6 7 8 →