Department of Medicine (Neurology), Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada.
Faculty of Engineering, Tokyo University of Science, Yamaguchi, Sanyo-onoda, Yamaguchi, Japan.
Trends Mol Med. 2017 Aug;23(8):709-720. doi: 10.1016/j.molmed.2017.06.003. Epub 2017 Jul 7.
Alzheimer'sdisease (AD) is a progressive neurodegenerative disorder, characterized by senile plaques constituting extracellular deposits of β-amyloid (Aβ) fibrils. Since Aβ accumulation in the brain is considered an early event preceding, by decades, cognitive dysfunction, disease-modifying treatments are aimed at facilitating clearance of this protein from the brain or ameliorating its toxic effects. Recent studies have identified the amylin receptor as a capable mediator of the deleterious actions of Aβ and furthermore, administration of amylin receptor-based peptides has been shown to improve spatial memory and learning in transgenic mouse models of AD. Here, by discussing available evidence, we posit that the amylin receptor could be considered a potential therapeutic target for AD, and present the rationale for using amylin receptor antagonists to treat this debilitating condition.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,其特征是由β-淀粉样蛋白(Aβ)原纤维构成的细胞外沉积物的老年斑。由于脑内 Aβ的积累被认为是认知功能障碍发生之前的早期事件,因此改变疾病进程的治疗方法旨在促进该蛋白从大脑中清除或改善其毒性作用。最近的研究已经确定了胰岛淀粉样肽受体作为 Aβ的有害作用的有效介质,此外,胰岛淀粉样肽受体衍生肽的给药已被证明可以改善 AD 转基因小鼠模型的空间记忆和学习能力。在这里,我们通过讨论现有证据,提出胰岛淀粉样肽受体可以被认为是 AD 的潜在治疗靶点,并提出使用胰岛淀粉样肽受体拮抗剂治疗这种使人衰弱的疾病的基本原理。