Word: presenilin
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Gamma secretase emerged as an attractive target shortly after 1995, when scientists working with DNA donated by families prone to early-onset Alzheimer's disease finally succeeded in cloning two genes known as presenilin 1 and presenilin 2. In a series of experiments, researchers established that these genes exercised tight control over the activity of gamma secretase. They found that the particular mutations in the Alzheimer's-prone families not only increased the rate at which gamma secretase produces beta amyloid but also enhanced its penchant for making the more toxic version...
Sometime later, two more early-onset Alzheimer's genes were found, Presenilin-1 and Presenilin-2. Like APP, these genes were dominant; a child who received just one gene from either parent would inevitably get the disease. One of the most tragic examples involved a 4,000-member Colombian family that had been haunted for generations by Alzheimer's. Yet such cases, researchers were only too well aware, accounted for merely a small fraction of all cases of Alzheimer's disease. Still other genes, they reasoned, must be involved in the great majority of cases--those in which dementia does...
...Selkoe, created yet another stir. They zeroed in on the elusive enzymes that snip the beta-amyloid fragment from the precursor protein. "We had the paper, and now we had the scissors," says Selkoe. If he is right, one of those scissors, gamma secretase, may actually be the presenilin-1 protein. Whatever the true identity of gamma secretase turns out to be, pharmaceutical companies are rushing to develop drugs that block it. Bristol-Myers Squibb has already started safety tests of one such compound and hopes to expand its study soon...
...research team reported in Thursday?s issue of the journal Nature that it had identified an enzyme, presenilin, that controls the production of a protein believed to be responsible for causing Alzheimer?s disease. Some 4 million Americans suffer from the debilitating memory loss. ?This is encouraging news for those afflicted with the devastating disease,? says TIME medical columnist Christine Gorman, ?but Alzheimer?s is still far from being conquered.? As with so many other medical discoveries, doctors and patients need to remain cautious. ?The report is significant from a research point of view,? says Gorman, ?but it needs...
...money to study things unless they think they have a good chance of developing a drug,? says Gorman. Thursday?s report gives encouragement that further study may eventually yield a payoff. But for now many questions still remain to be answered, not the least of which is this: If presenilin is indeed shown to be involved in causing Alzheimer?s disease, is it the only, the main or one of several causative factors...