School of Biomedical Sciences, Kent State University, Kent, USA.
Department of Biological Sciences, Kent State University, Kent, USA.
Curr Neuropharmacol. 2022;20(10):1894-1907. doi: 10.2174/1570159X19666211201093147.
The metabolic peptide hormone amylin, in concert with other metabolic peptides like insulin and leptin, has an important role in metabolic homeostasis and has been intimately linked to Alzheimer's disease (AD). Interestingly, this pancreatic amyloid peptide is known to self-aggregate much like amyloid-beta and has been reported to be a source of pathogenesis in both Type II diabetes mellitus (T2DM) and Alzheimer's disease. The traditional "gain of toxic function" properties assigned to amyloid proteins are, however, contrasted by several reports highlighting neuroprotective effects of amylin and a recombinant analog, pramlintide, in the context of these two diseases. This suggests that pharmacological therapies aimed at modulating the amylin receptor may be therapeutically beneficial for AD development, as they already are for T2DMM. However, the nature of amylin receptor signaling is highly complex and not well studied in the context of CNS function. Therefore, to begin to address this pharmacological paradox in amylin research, the goal of this review is to summarize the current research on amylin signaling and CNS functions and critically address the paradoxical nature of this hormone's signaling in the context of AD pathogenesis.
代谢肽激素胰淀素与胰岛素和瘦素等其他代谢肽一起，在代谢稳态中发挥着重要作用，并与阿尔茨海默病（AD）密切相关。有趣的是，这种胰腺淀粉样肽已知会像淀粉样-β一样自聚集，并已被报道是 2 型糖尿病（T2DM）和阿尔茨海默病发病机制的来源。然而，与传统的“毒性功能获得”特性相反的是，有几项报道强调了在这两种疾病中，胰淀素和重组类似物普兰林肽的神经保护作用。这表明，针对调节胰淀素受体的药物治疗可能对 AD 的发展具有治疗益处，就像它们对 T2DMM 一样。然而，在中枢神经系统功能方面，胰淀素受体信号转导的性质非常复杂，研究还不够深入。因此，为了解决胰淀素研究中的这种药理学悖论，本综述的目的是总结当前关于胰淀素信号转导和中枢神经系统功能的研究，并批判性地讨论该激素在 AD 发病机制中的信号转导的矛盾性质。
