Posted on 08/11/2006 9:51:04 AM PDT by neverdem
AP MEDICAL WRITER
WASHINGTON -- Scientists have discovered molecular janitors that clear away a sticky gunk blamed for Alzheimer's disease - until they get old and quit sweeping up.
The finding helps explain why Alzheimer's is a disease of aging. More importantly, it suggests a new weapon: drugs that give nature's cleanup crews a boost.
"It's a whole new way of thinking in the Alzheimer's field," said Dr. Andrew Dillin, a biologist at California's Salk Institute for Biological Studies who led the new research.
The discovery, published Thursday by the journal Science, was made in a tiny roundworm called C. elegans.
What do worms have to do with people? They're commonly used in age-related genetics research, and the new work involves a collection of genes that people harbor, too. Dillin's team from Salk and the neighboring Scripps Research Institute already is on the trail of potential drug candidates.
About 4.5 million Americans have Alzheimer's, a toll expected to more than triple by 2050 as the population grays. The creeping brain disease gradually robs sufferers of their memories and ability to care for themselves, eventually killing them. There is no known cure; today's drugs only temporarily alleviate symptoms.
Nor does anyone know what causes Alzheimer's. The lead suspect is a gooey protein called beta-amyloid. All brains contain it, although healthy cells somehow get rid of excess amounts. But beta-amyloid builds up in Alzheimer's patients, both inside their brain cells and forming clumps that coat the cells - plaque that is the disease's hallmark.
Thursday's study reveals one way that cells fend off amyloid buildup, and that natural aging gradually erodes that detoxification process.
"Every pathway we can discover that modifies amyloid provides us with new drug targets," said Dr. Sam Gandy, a neuroscientist at Philadelphia's Thomas Jefferson University and an Alzheimer's Association spokesman. "This now opens up a new pathway" for developing anti-Alzheimer's drugs.
Worms can't get Alzheimer's. So Dillin's team used roundworms that produce human beta-amyloid in the muscles of the body wall. As the worms age, amyloid builds up until it eventually paralyzes them; they can wiggle only their heads.
Then the researchers altered genes in a pathway called insulin/IGF-1, long known to be key in controlling lifespan. Making the worms live longer protected them from paralysis.
So in slowing down normal aging, something also slowed the buildup of toxic amyloid. But what?
Enter those cellular janitors, two proteins in that gene pathway.
One, named HSF-1, breaks apart amyloid and disposes of it, the researchers discovered. Natural aging slows HSF-1, so it can't keep up with the necessary detoxification.
Another protein called DAF-16 jumps in to help buy a little more time, by clumping extra amyloid together in a way that makes it less toxic.
That was a key finding, Dillin said: Until recently, scientists thought amyloid clumps, or plaques, were the bigger problem. His research supports more recent findings that smaller amyloid tendrils inside cells are the really poisonous form.
"We think probably the HSF-1 is the preferred way" to dispose of amyloid, Dillin said. "By the time you see the plaques, it's too late."
Mammals, including people, have these same proteins. Dillin now is repeating his experiment in mice to be sure they work the same way.
Scientists already are creating drugs to try to rid the brain of amyloid. These cleanup proteins point to a novel way to do that. The hope: Create drugs that boost their effects, and amyloid might not build up in the first place. Dillin said some initial drug attempts are showing promise in his worms.
The proteins won't be the brain's only natural amyloid scrubbers, noted Gandy, whose own research points toward involvement of another age-related gene.
The study is key for an additional reason, he added.
"We all knew that aging increases the risk for Alzheimer's," but not why, Gandy explained. "Now there's a direct link. ... It gives the molecular connection between aging and Alzheimer's."
And this process of "toxic aging" likely plays a role in still other neurodegenerative diseases, Dillin said, citing similar research with Huntington's disease.
>>Now if they could only remember what it was....
That's harsh, funny, but harsh.
I used to wonder if Kay's mother would have fared better if she hadn't stopped taking aspirin when she was young. (She had had a bad experience. She had put an aspirin in her mouth and then found there was nothing around to wash it down).
Kay's mother went through menopause at a very young age and was often "different" after that...irritable, suspicious, jealous. Kay is a very loving person (a saint!!), but her mother remained an angry person until the last months of her life, when she became able to accept love again.
Kay is grateful for that.
Wow: great news! Hope that this quickly leads to a good drug remedy.
"We all know that there will be no breakthroughs in Alzheimer's disease because President Bush has banned all research with Embryonic Stem Cells."
Thnk how the worms feel? Haven't read anything from PETA yet about this.
Just goes to show, there's always a silver lining.
Good heavens your RIGHT! I'm SHOCKED, SHOCKED I say, that we would sacrifice worms this way just so people wouldn't have to lose their personalities while their loved ones stand by helpless.
What are those selfish, speciest humans thinking. They should be banned like DDT.
Shalom.
Hot Dog!!! (my father has an "Alzheimers 'type' dementia called Picks Disease as well as Parkinson's disease)
Now notice the article has nothing to do with EMBRYONIC stem cell research. Michael J. Fox had my father so upset the other week. He has never been anything but liberal democrat anyway, but to hear everyone claim he (Bush) has the cure in his grasp!! He is just too fundamentalist to do it!!!!
I set him straight on that issue. I know he is still with me when we debate politics.
Any research to get people from thinking embryonic stem cells are going to cure Alzheimer's. That was not going to happen it was just a good PR move to get people to look at embryonic stem cell research with favor ability.
I have told my husband and son....if ever I do NOT recognize them due to Alzheimers....it's over.....take me on a little drive, in the snow.....let me wander off......I love snow.....
see post 36......and might I add...I do NOT feel the same way about being in a coma....people WAKE UP from coma's!
I will be going up tonight to help feed my grandmother, it is hard but I know that God is still in control and that suffering is part of life.
No need to wait for more drugs to be developed. There are natural products available now which detoxify the cells. My family and many people I know use these regularly and have seen amazing health benefits. One of the first benefits I experienced was brain chemistry balance. I believe most diseases could be prevented by the regular use of a good, natural cleanse product.
Thank you very much for this info. I had not heard of that. My ninety-three year old mother has senile dementia. They used to say it was Alzheimer's, but, thankfully, it is not progressing in that way.
Another tip: turmeric. There is lot of research now on how it might help break up amyloid plaques. I give my mom a good shot of it in her veggies each day.
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