Siew Jian Jing, Chern Yijuang, Khoo Kay-Hooi, Angata Takashi
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan; Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
Mol Aspects Med. 2023 Apr;90:101141. doi: 10.1016/j.mam.2022.101141. Epub 2022 Sep 9.
Microglia are resident myeloid cells in the central nervous system (CNS) with a unique developmental origin, playing essential roles in developing and maintaining the CNS environment. Recent studies have revealed the involvement of microglia in neurodegenerative diseases, such as Alzheimer's disease, through the modulation of neuroinflammation. Several members of the Siglec family of sialic acid recognition proteins are expressed on microglia. Since the discovery of the genetic association between a polymorphism in the CD33 gene and late-onset Alzheimer's disease, significant efforts have been made to elucidate the molecular mechanism underlying the association between the polymorphism and Alzheimer's disease. Furthermore, recent studies have revealed additional potential associations between Siglecs and Alzheimer's disease, implying that the reduced signal from inhibitory Siglec may have an overall protective effect in lowering the disease risk. Evidences suggesting the involvement of Siglecs in other neurodegenerative diseases are also emerging. These findings could help us predict the roles of Siglecs in other neurodegenerative diseases. However, little is known about the functionally relevant Siglec ligands in the brain, which represents a new frontier. Understanding how microglial Siglecs and their ligands in CNS contribute to the regulation of CNS homeostasis and pathogenesis of neurodegenerative diseases may provide us with a new avenue for disease prevention and intervention.
小胶质细胞是中枢神经系统（CNS）中的常驻髓样细胞，具有独特的发育起源，在中枢神经系统环境的发育和维持中发挥着重要作用。最近的研究表明，小胶质细胞通过调节神经炎症参与神经退行性疾病，如阿尔茨海默病。唾液酸识别蛋白Siglec家族的几个成员在小胶质细胞上表达。自从发现CD33基因多态性与晚发性阿尔茨海默病之间的遗传关联以来，人们为阐明该多态性与阿尔茨海默病之间关联的分子机制付出了巨大努力。此外，最近的研究揭示了Siglec与阿尔茨海默病之间的其他潜在关联，这意味着抑制性Siglec发出的信号减弱可能在降低疾病风险方面具有全面的保护作用。表明Siglec参与其他神经退行性疾病的证据也在不断涌现。这些发现有助于我们预测Siglec在其他神经退行性疾病中的作用。然而，对于大脑中功能相关的Siglec配体知之甚少，这是一个新的前沿领域。了解中枢神经系统中小胶质细胞Siglec及其配体如何有助于调节中枢神经系统稳态和神经退行性疾病的发病机制，可能为我们提供疾病预防和干预的新途径。
