A group of investigators report that it is possible to enhance insulin-degrading enzyme’s (IDE) ability to destroy amyloid beta (A-beta) with synthetic small molecules. In laboratory experiments, they found that one agent, dubbed Ia1, increased the activity of IDE by about 700%, while the second compound, Ia2, increased it by almost 400%.
The research, which is published in the April 22 online issue of PLoS ONE, was a collaboration between Mayo Clinic Florida, The Scripps Research Institute, and Harvard Medical School. The study is called “Small-Molecule Activators of Insulin-Degrading Enzyme Discovered through High-Throughput Compound Screening.”
IDE was the first degrading enzyme implicated in the imbalance seen between the production and elimination of A-beta in the brains of Alzheimer’s patients, according to lead researcher, Malcolm Leissring, Ph.D., from Mayo's department of neuroscience. “We don't know why that balance is skewed in individuals that develop Alzheimer's disease, but one hypothesis is that as we age, activity of the enzymes that destroy A-beta goes down.”
The scientists thus screened tens of thousands of chemicals looking for ones that could bind to IDE and modulate its activity. That led to discovery and testing of Ia1 and Ia2. Dr. Leissring says that the success they achieved in their test tube experiments offers a new path for more advanced research.
Past Alzheimer’s Research
Researchers Develop Standard of Testing for Alzheimer’s Biomarkers (3/18/2009)
Two Proteins Working in Tandem Leads to Amyloid Beta Buildup in Alzheimer’s (12/22/2008)
miRNA Implicated in Inflammation Integral to Alzheimer’s Disease (11/14/2008)
New Technique Able to Transport Potential Alzheimer’s and Stroke Treatment Past the Blood-Brain Barrier (11/12/2008)
Fatty-Acid Regulator Associated with Cognitive Function in Alzheimer’s Disease (10/28/2008)