Cornell and Harvard researchers discover mechanism that could lead to new treatments for Alzheimer's disease
While scientists already knew that the enzyme known as Pin1 can prevent the tangles of knotlike brain lesions associated with Alzheimer's, new research, published in Nature, finds the enzyme also plays a pivotal role in guarding against a second type of lesion, the buildup of plaque, or flat deposits on the surface of brain cells. Alzheimer's is caused by the two types of lesions, or alterations in brain tissue, occurring simultaneously. Researchers at Cornell University, Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School authored the study.
Linda Nicholson, co-principal investigator on the study and a Cornell associate professor of molecular biology and genetics, and her Cornell 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. Like a kind of molecular Dr. Jekyll and Mr. Hyde, one form leads to buildup 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 Hyde-like, 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 to block the pathway that leads to plaque buildup 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.
Nicholson and former graduate student Theresa Ramelot previously discovered the molecular switch in 2001. The new study with co-principal investigator Kun Ping Lu, an associate professor of medicine at Harvard Medical School, linked Pin1 and its action on this molecular switch directly to preventing both the tangle and plaque lesions. Lu and colleagues first identified the Pin1 enzyme in 1995.
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Topic World Spectroscopy
Investigation with spectroscopy gives us unique insights into the composition and structure of materials. From UV-Vis spectroscopy to infrared and Raman spectroscopy to fluorescence and atomic absorption spectroscopy, spectroscopy offers us a wide range of analytical techniques to precisely characterize substances. Immerse yourself in the fascinating world of spectroscopy!
Topic World Spectroscopy
Investigation with spectroscopy gives us unique insights into the composition and structure of materials. From UV-Vis spectroscopy to infrared and Raman spectroscopy to fluorescence and atomic absorption spectroscopy, spectroscopy offers us a wide range of analytical techniques to precisely characterize substances. Immerse yourself in the fascinating world of spectroscopy!