State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Int Immunopharmacol. 2023 Mar;116:109791. doi: 10.1016/j.intimp.2023.109791. Epub 2023 Feb 2.
The TAM receptors may help delay the progression of Alzheimer's disease (AD). AD is the most common neurodegenerative disease associated with human aging. The TAM receptors, derived from the first letter of its three constituents -Tyro3, Axl, and Mertk, are associated with immune responses, cellular differentiation and migration, and clearance of apoptotic cells and debris, with the two canonical ligands, Growth Arrest Specific 6 (Gas6) and ProS1. Several kinds of research have indicated the participation of the TAM system in AD pathology. Also, the TAMs regulate multiple features of microglia, the significant sensors of disorder in the central nervous system (CNS). In this review, we describe the biology of the TAM receptors and ligands in the CNS. Then, we discuss the relationship between the TAM system and AD, specially focusing on its functional expression in the microglia. Finally, we also summarize some agents that could interfere with the TAM signaling pathways and discuss potential difficulties and strategies for drug development.
TAM 受体可能有助于延缓阿尔茨海默病（AD）的进展。AD 是最常见的与人类衰老相关的神经退行性疾病。TAM 受体来源于其三个组成部分（Tyro3、Axl 和 Mertk）的首字母，与免疫反应、细胞分化和迁移以及凋亡细胞和碎片的清除有关，其两个典型配体为生长停滞特异性 6（Gas6）和 ProS1。许多研究表明 TAM 系统参与了 AD 病理学。此外，TAMs 调节小胶质细胞的多种特征，小胶质细胞是中枢神经系统（CNS）紊乱的重要传感器。在这篇综述中，我们描述了 TAM 受体和配体在中枢神经系统中的生物学特性。然后，我们讨论了 TAM 系统与 AD 的关系，特别是其在小胶质细胞中的功能表达。最后，我们还总结了一些可能干扰 TAM 信号通路的药物，并讨论了药物开发的潜在困难和策略。
