中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (12): 2565-2566.doi: 10.4103/NRR.NRR-D-23-01720

• 观点:退行性病与再生 • 上一篇    下一篇

tau片段的自组装是tau病的一个关键病理事件

  

  • 出版日期:2024-12-15 发布日期:2024-03-30

Self-assembly of tau fragments as a key pathologic event in tauopathies

Ly Thi Huong Luu Le#, Jung Hoon Lee#, Min Jae Lee*#br#   

  1. Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea
  • Online:2024-12-15 Published:2024-03-30
  • Contact: Min Jae Lee, PhD, minjlee@snu.ac.kr.
  • Supported by:
    This work was supported by grants from the National Research Foundation of Korea (2021R1A2C2008023, 2020R1A5A1019023, and RS-2023-00261784 to MJL; 2021R1I1A1A01051245 to JHL).

摘要: https://orcid.org/0000-0002-3252-6467 (Min Jae Lee)

Abstract: Tau protein is encoded by the microtubule-associated protein tau (MAPT) gene and stabilizes microtubules in the neurons. Tau has unique biophysical properties that make it both highly water-soluble and positively charged. Although tau is an intrinsically disordered protein lacking defined secondary structures, it can acquire highly organized -sheet structures and stack into a filamentous inclusion such as a paired helical filament (PHF). This is a common feature of tauopathies including Alzheimer’s disease (AD). The progression of tauopathies, both biochemically and symptomatically, is directly correlated with the extent of tau fibrillization. Extensive research has been conducted to determine the mechanisms underlying this phenomenon. A growing body of research indicates that genetic mutations linked to autosomal dominant tauopathies may be insufficient to cause significant conformational changes in tau. Instead, several post-translational modifications, including phosphorylation, acetylation, ubiquitylation, and O-GlcNAcylation, as well as their complex interaction, appear to play a crucial role in inducing fibrillization (Park et al., 2018; Kim et al., 2021). Tau phosphorylation, which weakens the electrostatic interactions between tau and axonal microtubules, has been a primary pharmacological target for AD treatment (Basheer et al., 2023). It has, however, failed to provide significant benefits for patients.