Geloso Maria Concetta, Ria Francesco, Corvino Valentina, Di Sante Gabriele
Section of Human Anatomy, Department of Neuroscience, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy.
Gemelli Science and Technology Park (GSTeP)-Organoids Research Core Facility, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.
Int J Mol Sci. 2025 Aug 24;26(17):8223. doi: 10.3390/ijms26178223.
CD44, a structurally diverse cell-surface glycoprotein, plays a multifaceted and indispensable role in neural tissue across both physiological and pathological conditions. It orchestrates complex cell-extracellular matrix interactions and intracellular signaling through its variant isoforms and post-translational modifications and is broadly expressed in neural stem/progenitor cells, microglia, astrocytes, and selected neuronal populations. The interactions of CD44 with ligands such as hyaluronan and osteopontin regulate critical cellular functions, including migration, differentiation, inflammation, and synaptic plasticity. In microglia and macrophages, CD44 mediates immune signaling and phagocytic activity, and it is dynamically upregulated in neuroinflammatory diseases, particularly through pathways involving Toll-like receptor 4. CD44 expression in astrocytes is abundant during central nervous system development and in diseases, contributing to glial differentiation, reactive astrogliosis, and scar formation. Though its expression is less prominent in mature neurons, CD44 supports neural plasticity, circuit organization, and injury-induced repair mechanisms. Additionally, its expression at nervous system barriers, such as the blood-brain barrier, underscores its role in regulating vascular permeability during inflammation and ischemia. Collectively, CD44 emerges as a critical integrator of neural cell function and intercellular communication. Although the roles of CD44 in glial cells appear to be similar to those explored in other tissues, the expression of this molecule and its variants on neurons reveals peculiar functions. Elucidating the cell-type-specific roles and regulation of CD44 variants may offer novel therapeutic strategies for diverse neurological disorders.
CD44是一种结构多样的细胞表面糖蛋白，在生理和病理条件下的神经组织中发挥着多方面且不可或缺的作用。它通过其可变剪接异构体和翻译后修饰协调复杂的细胞-细胞外基质相互作用和细胞内信号传导，并广泛表达于神经干/祖细胞、小胶质细胞、星形胶质细胞和特定的神经元群体中。CD44与透明质酸和骨桥蛋白等配体的相互作用调节关键的细胞功能，包括迁移、分化、炎症和突触可塑性。在小胶质细胞和巨噬细胞中，CD44介导免疫信号传导和吞噬活性，并且在神经炎症性疾病中动态上调，特别是通过涉及Toll样受体4的途径。星形胶质细胞中的CD44表达在中枢神经系统发育期间和疾病中丰富，有助于胶质细胞分化、反应性星形胶质细胞增生和瘢痕形成。尽管其在成熟神经元中的表达不太突出，但CD44支持神经可塑性、神经回路组织和损伤诱导的修复机制。此外，它在血脑屏障等神经系统屏障处的表达强调了其在炎症和缺血期间调节血管通透性的作用。总的来说，CD44成为神经细胞功能和细胞间通讯的关键整合者。尽管CD44在胶质细胞中的作用似乎与在其他组织中研究的作用相似，但该分子及其变体在神经元上的表达揭示了特殊的功能。阐明CD44变体的细胞类型特异性作用和调节可能为多种神经系统疾病提供新的治疗策略。
