In the fight against Alzheimer’s disease, the main culprit is a naturally occurring substance known as amyloid beta protein. These toxic proteins are self-assembling and quickly build up into a plaque in the brain that creates the symptoms commonly associated with Alzheimer’s like dementia and memory loss. Back in 2011, scientists began working on understanding these proteins in an effort to defeat them. Professor Richard Head from Australia’s Commonwealth Scientific and Industrial Research Organisation (CSIRO) said, “Before we can understand the processes involved in the deterioration of the brain, we must determine the molecular shape of the damaging protein. Until now this has proved incredibly difficult because of the protein’s propensity to self-assemble and clump together.”
What we now know about amyloid beta protein is that it is created when enzymes in the brain divide the much larger amyloid precursor protein (APP) into smaller sections. Sometimes when these proteins are broken down, two segments of APP protein join together in a process called dimerization – which ultimately results in the creation of amyloid protein. Scientists still don’t know why dimerization occurs, but they know that preventing it is the key to preventing the amyloid proteins from forming in the first place.
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That’s when Carmela Abraham, a professor of biochemistry and medicine at Boston University, came across one of 77,000 molecules that she believed could stop the process of dimerization. This molecule is what is known as a kinase inhibitor, which blocks the activity of kinase enzymes.
According to Abraham, “This was the big eureka moment. Once we knew what the molecule was doing, we could search to see what kinase it inhibits and better understand the mechanism.” If researchers can understand what inhibits kinase enzymes, they hope to be able to find the specific molecule that can prevent the enzymes that break up APP. If an inhibitor could be found that stops the enzymes that break up APP, Alzheimer’s disease could be stopped in its tracks. Abraham points out how important that really is: “Alzheimer’s is now the number six killer of adults in the United States. Deaths from breast cancer and heart disease keep dropping, but Alzheimer’s increases every year. Caring for Alzheimer’s patients costs over $200 billion dollars per year. The estimate for 2050 is $1.1 trillion, which means it will completely break the health care system. We have to find a drug.”
