Kim Sujin, Nam Yunkwon, Shin Soo Jung, Park Yong Ho, Jeon Seong Gak, Kim Jin-Il, Kim Min-Jeong, Moon Minho
Department of Biochemistry, College of Medicine, Konyang University, Daejeon, South Korea.
Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), Daegu, South Korea.
Front Neurosci. 2020 Sep 24;14:583097. doi: 10.3389/fnins.2020.583097. eCollection 2020.
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.
尽管阿尔茨海默病（AD）的主要致病因素是β-淀粉样蛋白的积累和tau蛋白的过度磷酸化，但AD也可能由代谢功能障碍引起。AD的主要临床症状是认知功能障碍。然而，AD还伴有各种继发症状，如抑郁、睡眠-觉醒障碍和异常饮食行为。有趣的是，促食欲激素胃饥饿素已被认为对AD相关的代谢综合征和继发症状具有有益作用。胃饥饿素可改善脂质分布并改变胰岛素敏感性，据推测这些作用可延缓AD的进展。此外，胃饥饿素可通过增强血清素、去甲肾上腺素和食欲素等激素的分泌来缓解抑郁。而且，胃饥饿素可上调脑源性神经营养因子等神经营养因子的表达，并调节肿瘤坏死因子α和白细胞介素1β等促炎细胞因子的释放。胃饥饿素通过增加褪黑素、促黑素的水平来减轻睡眠-觉醒障碍。胃饥饿素通过增加神经肽Y和γ-氨基丁酸来降低异常饮食行为的风险。此外，胃饥饿素通过抑制脂肪酸生物合成来增加食物摄入量。然而，尽管关于胃饥饿素在AD相关病理和代谢紊乱中的作用已有大量研究，但仅有少数研究探讨了胃饥饿素对AD相关继发症状的影响。在本综述中，我们的目的是通过整理先前关于胃饥饿素在AD相关病理和代谢紊乱中作用的研究，为未来的研究提供见解。
