Department of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Republic of Korea.
Department of Medical Science, Kyung Hee University, 23, Kyung Hee Dae-ro, Dongdaemun-gu, Seoul, Republic of Korea.
Ageing Res Rev. 2019 Nov;55:100945. doi: 10.1016/j.arr.2019.100945. Epub 2019 Aug 18.
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.
胃饥饿素具有许多重要的生理作用,如刺激食欲、调节能量平衡和释放胰岛素,最近它在各种神经紊乱中的作用也得到了研究。尽管胃饥饿素在中枢神经系统中有多种功能,但它是否可以作为神经功能障碍的治疗药物还不清楚。在阿尔茨海默病(AD)中,已经报道了胃饥饿素水平的改变和各种作用,AD 的特征是错误折叠的蛋白质积累导致突触丧失和认知能力下降。有趣的是,用胃饥饿素或胃饥饿素受体激动剂治疗在几种 AD 相关病理中显示出了缓解作用。这些发现表明胃饥饿素在 AD 发病机制中的潜在治疗意义。在本综述中,我们总结了胃饥饿素在 AD 发病机制、淀粉样β(Aβ)稳态、tau 过度磷酸化、神经炎症、线粒体缺陷、突触功能障碍和认知障碍中的作用。这些发现表明,胃饥饿素具有治疗 AD 的新的治疗潜力。因此,需要进行严格设计的研究来建立有效的 AD 治疗策略。