Clearance of the intracellular high level of the tau protein directed by an artificial synthetic hydrolase.

Promoting clearance of intracellular excessive tau is a potential therapeutic strategy for treating Alzheimer's disease. In this work, we designed and synthesized a cyclen-hybrid artificial 'hydrolase' I1-Cu(II) to cleave tau in vitro. Furthermore, a cell-permeable 'hydrolase' I2-Cu(II), derived from I1-Cu(II), was also synthesized to cleave intracellular tau proteins.