한빛사 논문
Seong Gak Jeona,1, Sang Bum Honga,1, Yunkwon Nama,1, Jungyeon Taea, Anji Yooa, Eun Ji Songa, Kun Il Kima, Dongje Leea, Junyong Parka, Sang Min Leeb, Jin-il Kimc,*, Minho Moona,*
a Department of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Republic of Korea
b Department of Medical Science, Kyung Hee University, 23, Kyung Hee Dae-ro, Dongdaemun-gu, Seoul, Republic of Korea
c Department of Nursing, College of Nursing, Jeju National University, Jeju 63243, Republic of Korea
*Corresponding authors : Jin-il Kim, Minho Moon
1These authors contributed equally to this work.
Abstract
Ghrelin, which has many important physiological roles, such as stimulating food intake, regulating energy homeostasis, and releasing insulin, has recently been studied for its roles in a diverse range of neurological disorders. Despite the several functions of ghrelin in the central nervous system, whether it works as a therapeutic agent for neurological dysfunction has been unclear. Altered levels and various roles of ghrelin have been reported in Alzheimer’s disease (AD), which is characterized by the accumulation of misfolded proteins resulting in synaptic loss and cognitive decline. Interestingly, treatment with ghrelin or with the agonist of ghrelin receptor showed attenuation in several cases of AD-related pathology. These findings suggest the potential therapeutic implications of ghrelin in the pathogenesis of AD. In the present review, we summarized the roles of ghrelin in AD pathogenesis, amyloid beta (Aβ) homeostasis, tau hyperphosphorylation, neuroinflammation, mitochondrial deficit, synaptic dysfunction and cognitive impairment. The findings from this review suggest that ghrelin has a novel therapeutic potential for AD treatment. Thus, rigorously designed studies are needed to establish an effective AD-modifying strategy.
Abbreviations
AD, Alzheimer’s disease; AChE, acetylcholinesterase; acyl-ghrelin, acylated ghrelin; AMPK, AMP-induced protein kinase; apo, apolipoprotein; APP, amyloid precursor protein; ARC, arcuate nucleus; Aβ, amyloid beta; AβO, Aβ oligomers; BBB, blood-brain barrier; BDNF, brain-derived neurotrophic factor; CaMKII, Ca2+/calmodulin-dependent protein kinase II; CDK, cyclin-dependent kinase; CNS, central nervous system; DG, dentate gyrus; DRN, dorsal raphe nucleus; ERK, extracellular-signal-regulated kinase; FACS, fluorescence activated cell sorting; GABA, γ-aminobutyric acid; GHS-R, growth hormone secretagogue-receptor; GHRP-6, growth hormone-releasing peptide 6; GKO, ghrelin knockout; GOAT, O-acyltransferase; GPCR, G-protein-coupled receptor; GSK, glycogen synthase kinase; i.c.v, intracerebroventricular; IGF-1, insulin-like growth factor 1; IL, interleukin; LPS, lipopolysaccharide; LRP, low density lipoprotein receptor-related protein; LTD, long-term depression; LTP, long-term potentiation; MACRO, macrophage receptor with collagenous structure; MAPK, mitogen-activated protein kinase; MCI, mild cognitive impairment; MPTP, 1-methyl-4-phenyl-12,3,6-tetrahydropyridine; MSG, monosodium l-glutamate; NSC, neural stem cell; NFT, neurofibrillary tangles; NMDA, N-methyl d-aspartate; p75NT, p75 neurotrophin; PD, Parkinson’s disease; PI3-K, phosphoinositide 3-kinase; PLC, phospholipase C; RAGE, receptor for advanced glycation end products; ROS, reactive oxygen species; SGZ, subgranular zone; UCP2, uncoupling protein 2; α2M, α2-macroglobulin
Keywords : Ghrelin; Alzheimer’s disease; Amyloid beta; Tau; Mitochondrial deficits; Neuroinflammation
논문정보
관련 링크
연구자 ID
관련분야 연구자보기
관련분야 논문보기