中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (7): 2958-2959.doi: 10.4103/NRR.NRR-D-25-00869

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

颗粒蛋白前体:剂量依赖性的神经毒性

  

  • 出版日期:2026-07-15 发布日期:2026-03-27

Progranulin: Dose-dependent neurotoxicity

Shinya Kusakari, Kohsuke Kanekura*   

  1. Department of Pharmacology, Tokyo Medical University, Tokyo, Japan
  • Online:2026-07-15 Published:2026-03-27
  • Contact: Kohsuke Kanekura, MD, PhD, kanekura@tokyo-med.ac.jp.
  • Supported by:
    This work was supported by SENSHIN Medical Research Foundation, Takeda Science Foundation, Taiju Life Social Welfare Foundation, Mitsui Sumitomo Insurance Welfare Foundation, Research Foundation for Pharmaceutical Sciences, Tokyo Medical University Research Grant, JSPS KAKENHI (23K06369) to SK, and JSPS KAKENHI (24K02187) to KK.

摘要: https://orcid.org/0000-0002-2901-9595 (Kohsuke Kanekura)
 

Abstract: Progranulin (PGRN), encoded by the GRN gene, is a secreted glycoprotein that undergoes proteolytic cleavage to generate individual granulin peptides (granulin A–G) capable of exerting distinct biological functions. PGRN is widely expressed in multiple tissues, including the central nervous and immune systems. Within the central nervous system, PGRN is highly expressed in the hippocampus, cerebral cortex, and hypothalamus, and has been detected in various neuronal subtypes, including Purkinje cells and motor neurons, where it plays a crucial role in neuronal functions, such as neurite outgrowth and synaptic plasticity. In addition to neurons, PGRN is expressed in glial cells, particularly in microglia, where it regulates phagocytosis. Furthermore, PGRN is presented in peripheral immune cells, including macrophages, and contributes to the regulation of inflammatory responses. PGRN exerts its diverse functions via binding partners, including receptors such as sortilin, EphA2, Notch, death receptor 3, and toll-like receptor 9 (Chitramuthu et al., 2017). These interactions underlie the involvement of PGRN in a wide range of cellular processes, including proliferation, differentiation, migration, immune regulation, and tumorigenesis. For instance, the interaction of PGRN with sortilin participates in the endocytosis and lysosomal trafficking of PGRN, whereas Notch signaling influences cell fate decisions and has implications for both neural development and oncogenesis (Chitramuthu et al., 2017).