Eskandari-Sedighi Ghazaleh, Jung Jaesoo, Macauley Matthew S
Department of Chemistry, University of Alberta, Canada.
Department of Chemistry, University of Alberta, Canada; Department of Medical Microbiology and Immunology, University of Alberta, Canada.
Mol Aspects Med. 2023 Apr;90:101111. doi: 10.1016/j.mam.2022.101111. Epub 2022 Aug 5.
Alzheimer's disease (AD) is the most common form of neurodegenerative disease and is considered the main cause of dementia worldwide. Genome-wide association studies combined with integrated analysis of functional datasets support a critical role for microglia in AD pathogenesis, identifying them as important potential therapeutic targets. The ability of immunomodulatory receptors on microglia to control the response to pathogenic amyloid-β aggregates has gained significant interest. Siglec-3, also known as CD33, is one of these immunomodulatory receptors expressed on microglia that has been identified as an AD susceptibility factor. Here, we review recent advances made in understanding the multifaceted roles that CD33 plays in microglia with emphasis on two human-specific CD33 isoforms that differentially correlate with AD susceptibility. We also describe several different therapeutic approaches for targeting CD33 that have been advanced for the purpose of skewing microglial cell responses.
阿尔茨海默病（AD）是最常见的神经退行性疾病形式，被认为是全球痴呆症的主要病因。全基因组关联研究与功能数据集的综合分析支持小胶质细胞在AD发病机制中起关键作用，将它们确定为重要的潜在治疗靶点。小胶质细胞上的免疫调节受体控制对致病性淀粉样β聚集体反应的能力引起了极大关注。唾液酸结合免疫球蛋白样凝集素3（Siglec-3），也称为CD33，是这些在小胶质细胞上表达的免疫调节受体之一，已被确定为AD易感性因素。在此，我们综述了在理解CD33在小胶质细胞中所起的多方面作用方面取得的最新进展，重点关注与AD易感性有不同关联的两种人类特有的CD33异构体。我们还描述了几种针对CD33的不同治疗方法，这些方法已被提出用于改变小胶质细胞反应。
