Hyaluronidase: structure, mechanism of action, diseases and therapeutic targets

作者：Jian R. Lu, Zheng Zhao, Lingli Pan, Hui Wu, Shibing Wang, Xiangmin Tong, Shiliang Wu · 发表于：Molecular Biomedicine · 年份：2025 · DOI：10.1186/s43556-025-00299-y · 被引用次数：51 · 研究领域：Proteoglycans and glycosaminoglycans research、Peptidase Inhibition and Analysis、Protease and Inhibitor Mechanisms

Hyaluronidase (HAase), a family of enzymes critical for regulating physiological and pathological states, catalyzes the degradation of hyaluronic acid (HA), a key component of the extracellular matrix (ECM). By modulating ECM composition and cellular signaling pathways, HAase plays a pivotal role in diverse biological processes, including wound healing, tissue regeneration, and tumor progression. This review systematically elucidates the classification, biological sources, structural diversity, and catalytic mechanisms of HAase, emphasizing its dynamic involvement in disease pathogenesis and diagnostic potential. Furthermore, the article explores innovative therapeutic strategies centered on HAase modulation. HAase inhibitors emerge as promising tools for maintaining HA homeostasis, with implications in anti-inflammatory, antimicrobial, and antitumor therapies by blocking excessive HA degradation. Concurrently, HAase-mediated drug delivery systems represent a paradigm shift in overcoming biological barriers, enhancing bioavailability, and optimizing therapeutic outcomes through ECM remodeling. Notably, the synergy between HAase and immunotherapeutic modalities, such as checkpoint inhibitors and adoptive cell therapies, demonstrates synergistic antitumor effects by reshaping the tumor microenvironment (TME) and augmenting immune cell infiltration. Nevertheless, numerous challenges persist in the clinical application of hyaluronidase, including its immunogenicity, safety, appli...