Protein Inhibitor Tangles With Alzheimer's Disease

The study appears online on February 15 in advance of publication in the March print issue of the Journal of Clinical Investigation.

A hallmark of AD is the abnormal accumulation of phosphorylated tau (p-tau) proteins resulting in the formation of neurofibrillary tangles, which impair the function of brain axons. Enhancing the removal of these p-tau proteins may therefore be a relevant therapeutic strategy.

In the current study, Leonard Petrucelli and colleagues from the Mayo Clinic showed that a complex of two proteins, CHIP and Hsp90 (which are involved in protein refolding and degradation), plays a role in alleviating p-tau accumulation in mice and cultured human cells. They went on to show that administration of an Hsp90 inhibitor, EC102, to mice overexpressing human tau caused a significant reduction in p-tau levels.

The findings point to a pivotal role for Hsp90 in aberrant tau degradation and potentially in tau refolding. Unlike many drugs, EC102 is able to cross the blood-brain barrier, making it a highly promising therapeutic candidate for AD and other conditions in which tau accumulates in abnormally high levels in the brain.