Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an 710061, China; Institute of Neurobiology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an 710061, China.
Neuropeptides. 2019 Feb;73:96-106. doi: 10.1016/j.npep.2018.12.003. Epub 2018 Dec 18.
Alzheimer's disease (AD) is one of the major disabling and lethal diseases for aged individuals worldwide. To date, there are more than 10 hypotheses proposed for AD pathology. The beta-amyloid (Aβ) cascade hypothesis is the most widely accepted and proposes that the accumulation of Aβ in the brain is one potential mechanism for AD pathogenesis. Because some Aβ-overloaded patients do not have AD syndrome, this hypothesis is challenged from time to time. More recently, it has been shown that intracellular Aβ plays a key role in AD pathology. Aβ is internalized by receptors distributed on the cell membrane. Among these receptors, the alpha7 nicotinic acetylcholine receptor (α7 nAChR) has been shown to play an important role in AD. The α7 nAChR is a ligand-gated ion channel and is expressed in pivotal brain regions (e.g., the cerebral cortex and hippocampus) responsible for cognitive functions. The α7 nAChR is localized both presynaptically and postsynaptically, where it activates intracellular signaling cascades. Its agonist has been investigated in clinical studies to improve cognitive functions in AD. Although many studies have shown the importance of the α7 nAChR in AD, little is known regarding its role in AD pathology. Therefore, in the current review, we summarized the basic information regarding the structures and functions of the α7 nAChR, the distribution and expression of the α7 nAChR, and the role of the α7 nAChR in mediating Aβ internalization. We subsequently focused on introducing the comprehensive α7 nAChR related signaling pathways and how these signaling pathways are integrated with the α7 nAChR to play a role in AD. Finally, we stressed the AD therapy that targets the α7 nAChR.
阿尔茨海默病（AD）是全球老年人致残和致死的主要疾病之一。迄今为止，已经提出了超过 10 种 AD 病理学假说。β-淀粉样蛋白（Aβ）级联假说被广泛接受，该假说提出 Aβ在大脑中的积累是 AD 发病机制的一个潜在机制。由于一些 Aβ超负荷的患者没有 AD 综合征，因此该假说不时受到挑战。最近，研究表明细胞内 Aβ在 AD 病理学中起关键作用。Aβ被分布在细胞膜上的受体内化。在这些受体中，α7 烟碱型乙酰胆碱受体（α7 nAChR）已被证明在 AD 中发挥重要作用。α7 nAChR 是一种配体门控离子通道，在负责认知功能的关键脑区（如大脑皮层和海马体）中表达。α7 nAChR 位于突触前和突触后，在那里它激活细胞内信号级联。其激动剂已在临床研究中进行了研究，以改善 AD 的认知功能。尽管许多研究表明 α7 nAChR 在 AD 中的重要性，但对其在 AD 病理学中的作用知之甚少。因此，在本综述中，我们总结了有关 α7 nAChR 的结构和功能、α7 nAChR 的分布和表达以及 α7 nAChR 在介导 Aβ内化中的作用的基本信息。随后，我们重点介绍了全面的 α7 nAChR 相关信号通路以及这些信号通路如何与 α7 nAChR 整合以在 AD 中发挥作用。最后，我们强调了针对 α7 nAChR 的 AD 治疗。
