Tethered Inhibitor More Effective for Alzheimer's

Inhibitor tethered to cell membrane; could be new approach to drug development

FRIDAY, April 25 (HealthDay News) -- An inhibitor of an Alzheimer's disease target that is tethered to the cell membrane is more effective than the free inhibitor, and the approach could be used to design more effective inhibitors, according to a study in the April 25 issue of Science.

Lawrence Rajendran from the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, and colleagues examined the activity of a membrane-anchored soluble inhibitor of the beta-secretase enzyme.

The researchers found that the membrane-anchored inhibitor was more effective than the free inhibitor in inhibiting the cleavage of amyloid precursor protein (APP) by beta-secretase. The membrane-bound inhibitor was transported to endosomes, where APP is found, by endocytosis. The membrane-bound inhibitor was effective in reducing the production of beta-amyloid peptide in a fly model of Alzheimer's disease as well as in normal mice.

"This work represents a proof-of-principle for a new approach in the design of more effective beta-secretase inhibitors for the treatment of Alzheimer's disease," Rajendran and colleagues conclude.

Three authors report relationships with Jado Technologies.

Abstract
Full Text (subscription or payment may be required)

Physician's Briefing