Soares Luana C, Al-Dalahmah Osama, Hillis James, Young Christopher C, Asbed Isaiah, Sakaguchi Masanori, O'Neill Eric, Szele Francis G
Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, South Parks Road, Oxford OX1 3QX, UK.
Department of Oncology, University of Oxford, Oxford OX1 3QX, UK.
Cells. 2021 Nov 5;10(11):3047. doi: 10.3390/cells10113047.
Galectin-3 (Gal-3) is an evolutionarily conserved and multifunctional protein that drives inflammation in disease. Gal-3's role in the central nervous system has been less studied than in the immune system. However, recent studies show it exacerbates Alzheimer's disease and is upregulated in a large variety of brain injuries, while loss of Gal-3 function can diminish symptoms of neurodegenerative diseases such as Alzheimer's. Several novel molecular pathways for Gal-3 were recently uncovered. It is a natural ligand for TREM2 (triggering receptor expressed on myeloid cells), TLR4 (Toll-like receptor 4), and IR (insulin receptor). Gal-3 regulates a number of pathways including stimulation of bone morphogenetic protein (BMP) signaling and modulating Wnt signalling in a context-dependent manner. Gal-3 typically acts in pathology but is now known to affect subventricular zone (SVZ) neurogenesis and gliogenesis in the healthy brain. Despite its myriad interactors, Gal-3 has surprisingly specific and important functions in regulating SVZ neurogenesis in disease. Gal-1, a similar lectin often co-expressed with Gal-3, also has profound effects on brain pathology and adult neurogenesis. Remarkably, Gal-3's carbohydrate recognition domain bears structural similarity to the SARS-CoV-2 virus spike protein necessary for cell entry. Gal-3 can be targeted pharmacologically and is a valid target for several diseases involving brain inflammation. The wealth of molecular pathways now known further suggest its modulation could be therapeutically useful.
半乳糖凝集素-3（Gal-3）是一种进化上保守的多功能蛋白质，在疾病中引发炎症。与免疫系统相比，Gal-3在中枢神经系统中的作用研究较少。然而，最近的研究表明，它会加剧阿尔茨海默病，并且在多种脑损伤中上调，而Gal-3功能丧失可减轻诸如阿尔茨海默病等神经退行性疾病的症状。最近发现了几种Gal-3的新分子途径。它是髓系细胞上表达的触发受体（TREM2）、Toll样受体4（TLR4）和胰岛素受体（IR）的天然配体。Gal-3调节多种途径，包括刺激骨形态发生蛋白（BMP）信号传导，并以上下文依赖的方式调节Wnt信号传导。Gal-3通常在病理学中起作用，但现在已知它会影响健康大脑中的脑室下区（SVZ）神经发生和神经胶质生成。尽管Gal-3有众多相互作用分子，但它在调节疾病中的SVZ神经发生方面具有令人惊讶的特定且重要的功能。Gal-1是一种经常与Gal-3共表达的类似凝集素，对脑病理学和成年神经发生也有深远影响。值得注意的是，Gal-3的碳水化合物识别结构域与细胞进入所必需的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒刺突蛋白具有结构相似性。Gal-3可以通过药物靶向，并且是几种涉及脑炎症疾病的有效靶点。现在已知的丰富分子途径进一步表明，对其进行调节可能具有治疗作用。
