Right target, but missing the bulls-eye for Alzheimer's

Right target, but missing the bulls-eye for Alzheimer's

UCLA researchers discover new point of attack for drug therapy

Abeta hairpin
Abeta, with hairpin turn between orange and red arrows
Alzheimer's disease is the most common cause of late-life dementia. The disorder is thought to be caused by a protein known as amyloid-beta, or Abeta, which clumps together in the brain, forming plaques that are thought to destroy neurons. This destruction starts early, too, and can presage clinical signs of the disease by up to 20 years.
 
For decades now, researchers have been trying, with limited success, to develop drugs that prevent this clumping. Such drugs require a "target" — a structure they can bind to, thereby preventing the toxic actions of Abeta.
 
Now, a new study out of UCLA suggests that while researchers may have the right target in Abeta, they may be missing the bull's-eye. Reporting in the Jan. 23 issue of the Journal of Molecular Biology, UCLA neurology professor David Teplow and colleagues focused on a particular segment of a toxic form of Abeta and discovered a unique hairpin-like structure that facilitates clumping.
 
"Every 68 seconds, someone in this country is diagnosed with Alzheimer's," said Teplow, the study's senior author and principal investigator of the NIH-sponsored Alzheimer's Disease Research Center at UCLA. "Alzheimer's disease is the only one of the top 10 causes of death in America that cannot be prevented, cured or even slowed down once it begins. Most of the drugs that have been developed have either failed or only provide modest improvement of the symptoms. So finding a better pathway for these potential therapeutics is critical."
 

UCTV on Alzheimer's

UCTV David Teplow screenshot

This three-part series reveals the heartache for those suffering from and coping with Alzheimer's disease and the hope offered by UCLA researchers leading the charge to slow its progress and, eventually, find a cure. The series also profiles a growing network of caregiver support groups established by Patti Davis, daughter of President Ronald Reagan, and television personality Leeza Gibbons, who lost her mother to the disease.

UCTV on Alzheimer's

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UCLA researchers determine toxicity levels of Alzheimer's clusters in brain

Findings provide target for new classes of therapeutic drugs.

Scientists have long suspected that Alzheimer's disease is caused by plaques formed when the small protein amyloid-beta (Aß) binds to itself in clusters and undergoes a chemical change, creating protein deposits in the brain.

However, recent studies have suggested it is not the plaques that cause Alzheimer's but the small, grape-like clusters of Aß. The clusters vary in size, and the relationship between cluster size and toxicity — the ability to kill nerve cells — has never been determined accurately.

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Red, red wine: How it fights Alzheimer's

Researchers discover how compounds found in wine thwart disease in mice

Scientists call it the "French paradox" — a society that, despite consuming food high in cholesterol and saturated fats, has long had low death rates from heart disease. Research has suggested it is the red wine consumed with all that fatty food that may be beneficial — and not only for cardiovascular health but in warding off certain tumors and even Alzheimer's disease.

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Getting Out of the Loop of Alzheimer's Disease

Scientists from UCLA recently pinpointed a possible physical origin of Alzheimer's disease. The amyloid-beta protein has long been known to clump in the brain and be involved in the progression of the disease. The UCLA team identified a loop in the protein that is likely to enable amyloid-beta's adhesion process. This discovery suggests new ways to treat the disorder's cause, rather than just the symptoms.

Alzheimer's disease (AD) is the most common cause of late-life dementia. It is estimated to affect 24 million people worldwide, and half of the people over 85 may suffer from it. This fatal disorder is characterized by a decline in the individuals' memory and in their ability to think and function independently. Current drugs treat the symptoms of Alzheimer's but not the underlying cause of the disease.

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