Enzyme Prevents from Plaque Build-Up -- MEDICA - World Forum for Medicine

While scientists already knew that the enzyme known as Pin1 can prevent the tangles of knotlike brain lesions associated with Alzheimer's, new research finds the enzyme also plays a pivotal role in guarding against a second type of lesion, the build-up of plaque on the surface of brain cells. Alzheimer's is caused by the two types of lesions, or alterations in brain tissue, occurring simultaneously.

"The new finding provides a very specific molecular interaction that can be used as a target in drug discovery," said Linda Nicholson, co-principal investigator on the study and a Cornell associate professor of molecular biology and genetics.

Nicholson and her team observed Pin1 acting on a protein called amyloid precursor protein (APP), which appears to be the primary cause of Alzheimer's. When APP gets a phosphate group attached to its tail, it toggles slowly back and forth between two forms. One form leads to build-up of plaque and disease, while the other form is part of normal function and helps neurons grow and survive.

Using nuclear magnetic resonance spectroscopy, Nicholson and colleagues found that Pin1 acts as a kind of molecular accelerator, allowing APP to toggle back and forth between its good and bad forms 1,000 times faster than if Pin1 were not present. In the absence of Pin1, the disease-causing form of APP has a chance to build up to high levels toxic to cells, which leads to plaque lesions.

"The really important thing here is that this research opens up entirely new therapeutic approaches to treating Alzheimer's," said Nicholson.

One therapy might be to create small molecules that resemble the bad form of APP, which could then flood receptors and hinder the pathway, she said. Another way might be to create a molecule that attaches to this form of APP, which would also prevent binding to receptor sites, thereby interrupting the pathway.

MEDICA.de; Source: Cornell University