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Protein Inhibitor Tangles With Alzheimer's Disease

Date:
February 18, 2007
Source:
Journal of Clinical Investigation
Summary:
A hallmark of Alzheimer's disease (AD) is the abnormal accumulation of phosphorylated forms of a protein known as tau. In a new study, Mayo Clinic researchers have now shown in mice that a drug that inhibits the function of the protein Hsp90 (EC102) reduces the amount of phosphorylated tau in the brain. Unlike many drugs, EC102 is able to cross the blood-brain barrier, making it a highly promising therapeutic candidate for AD.
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Mayo Clinic researchers have now shown that a drug that inhibits the function of the protein Hsp90 reduces brain levels in mice of the protein tau, the abnormal accumulation of which has been implicated in the pathogenesis of Alzheimer's disease (AD).

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.


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Journal of Clinical Investigation. "Protein Inhibitor Tangles With Alzheimer's Disease." ScienceDaily. ScienceDaily, 18 February 2007. <www.sciencedaily.com/releases/2007/02/070215181509.htm>.
Journal of Clinical Investigation. (2007, February 18). Protein Inhibitor Tangles With Alzheimer's Disease. ScienceDaily. Retrieved May 25, 2017 from www.sciencedaily.com/releases/2007/02/070215181509.htm
Journal of Clinical Investigation. "Protein Inhibitor Tangles With Alzheimer's Disease." ScienceDaily. www.sciencedaily.com/releases/2007/02/070215181509.htm (accessed May 25, 2017).

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