Division of Neuroanatomy, Department of Anatomy, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi 467-8603, Japan.
Neurosci Res. 2024 Nov;208:8-14. doi: 10.1016/j.neures.2024.07.004. Epub 2024 Jul 31.
Alzheimer's disease (AD) is the most prevalent type of dementia; therefore, there is a high demand for therapeutic medication targeting it. In this context, extensive research has been conducted to identify molecular targets for drugs. AD manifests through two primary pathological signs: senile plaques and neurofibrillary tangles, caused by accumulations of amyloid-beta (Aβ) and phosphorylated tau, respectively. Thus, studies concerning the molecular mechanisms underlying AD etiology have primarily focused on Aβ generation and tau phosphorylation, with the anticipation of uncovering a signaling pathway impacting these molecular processes. Over the past two decades, studies using not only experimental model systems but also examining human brains have accumulated fragmentary evidences suggesting that REELIN signaling pathway is deeply involved in AD. Here, we explore REELIN signaling pathway and its involvement in memory function within the brain and review studies investigating molecular connections between REELIN signaling pathway and AD etiology. This review aims to understand how the manipulation (activation) of this pathway might ameliorate the disease's etiology.
阿尔茨海默病（AD）是最常见的痴呆症类型；因此，对针对它的治疗药物有很高的需求。在这种情况下，已经进行了广泛的研究以确定药物的分子靶标。AD 通过两种主要的病理标志表现出来：老年斑和神经原纤维缠结，分别由淀粉样蛋白-β（Aβ）和磷酸化 tau 的积累引起。因此，有关 AD 病因的分子机制的研究主要集中在 Aβ 的产生和 tau 的磷酸化上，以期发现影响这些分子过程的信号通路。在过去的二十年中，不仅使用实验模型系统，而且还研究了人类大脑的研究积累了零碎的证据表明，REELIN 信号通路与 AD 密切相关。在这里，我们探讨了 REELIN 信号通路及其在大脑内记忆功能中的作用，并回顾了研究 REELIN 信号通路与 AD 病因之间分子联系的研究。本综述旨在了解如何操纵（激活）该通路可能改善疾病的病因。
