Reich Niklas, Hölscher Christian
Biomedical & Life Sciences Division, Lancaster University, Lancaster, United Kingdom.
Neurology Department, A Second Hospital, Shanxi Medical University, Taiyuan, China.
Front Neurosci. 2020 Dec 14;14:614828. doi: 10.3389/fnins.2020.614828. eCollection 2020.
Much thought has been given to the impact of Amyloid Beta, Tau and Alpha-Synuclein in the development of Alzheimer's disease (AD) and Parkinson's disease (PD), yet the clinical failures of the recent decades indicate that there are further pathological mechanisms at work. Indeed, besides amyloids, AD and PD are characterized by the culminative interplay of oxidative stress, mitochondrial dysfunction and hyperfission, defective autophagy and mitophagy, systemic inflammation, BBB and vascular damage, demyelination, cerebral insulin resistance, the loss of dopamine production in PD, impaired neurogenesis and, of course, widespread axonal, synaptic and neuronal degeneration that leads to cognitive and motor impediments. Interestingly, the acylated form of the hormone ghrelin has shown the potential to ameliorate the latter pathologic changes, although some studies indicate a few complications that need to be considered in the long-term administration of the hormone. As such, this review will illustrate the wide-ranging neuroprotective properties of acylated ghrelin and critically evaluate the hormone's therapeutic benefits for the treatment of AD and PD.
人们已经对β-淀粉样蛋白、 Tau蛋白和α-突触核蛋白在阿尔茨海默病(AD)和帕金森病(PD)发展中的影响进行了大量思考,但近几十年来的临床失败表明,还有其他病理机制在起作用。事实上,除了淀粉样蛋白外,AD和PD的特征还包括氧化应激、线粒体功能障碍和过度分裂、自噬和线粒体自噬缺陷、全身炎症、血脑屏障和血管损伤、脱髓鞘、脑胰岛素抵抗、PD中多巴胺生成减少、神经发生受损,当然还有广泛的轴突、突触和神经元变性,这些都会导致认知和运动障碍。有趣的是,酰化形式的胃饥饿素已显示出改善后者病理变化的潜力,尽管一些研究表明,在长期使用该激素时需要考虑一些并发症。因此,本综述将阐述酰化胃饥饿素广泛的神经保护特性,并批判性地评估该激素对AD和PD治疗的益处。