Max-Planck-Unit for Structural Molecular Biology c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany.
Biochem Soc Trans. 2010 Aug;38(4):955-61. doi: 10.1042/BST0380955.
Tau aggregation is a hallmark of several neurodegenerative diseases, including AD (Alzheimer's disease), although the mechanism underlying tau aggregation remains unclear. Recent studies show that the proteolysis of tau plays an important role in both tau aggregation and neurodegeneration. On one hand, truncation of tau may generate amyloidogenic tau fragments that initiate the aggregation of tau, which in turn can cause toxicity. On the other hand, truncation of tau may result in tau fragments which induce neurodegeneration through unknown mechanisms, independently of tau aggregation. Blocking the truncation of tau thus may represent a promising therapeutic approach for AD or other tauopathies. In the present paper, we summarize our data on tau cleavage in a cell model of tauopathy and major results on tau cleavage reported in the literature.
tau 聚集是包括 AD（阿尔茨海默病）在内的几种神经退行性疾病的标志，尽管 tau 聚集的机制尚不清楚。最近的研究表明，tau 的蛋白水解在 tau 的聚集和神经退行性变中都起着重要作用。一方面，tau 的截断可能会产生淀粉样蛋白 tau 片段，从而引发 tau 的聚集，进而导致毒性。另一方面，tau 的截断可能会导致 tau 片段通过未知机制引发神经退行性变，而不依赖于 tau 的聚集。因此，阻止 tau 的截断可能代表着 AD 或其他 tau 病的一种有前途的治疗方法。在本文中，我们总结了 tau 病细胞模型中 tau 切割的我们的数据和文献中报道的 tau 切割的主要结果。
