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A Synthetic Peptide Destroys Brain Plaque Implicated In Alzheimer's Disease

Date:
July 2, 1998
Source:
New York University Medical Center And School Of Medicine
Summary:
New York University School of Medicine researchers have created a protein fragment that blocks the formation of a substance implicated in causing Alzheimer's disease, a finding that may lay the foundation for a novel therapy for the mind robbing disease.
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New York, NY- June 29, 1998-- New York University School of Medicine researchers have created a protein fragment that blocks the formation of a substance implicated in causing Alzheimer's disease, a finding that may lay the foundation for a novel therapy for the mind robbing disease.

Alzheimer's disease is characterized by the destruction of nerve cells, especially in the areas of the brain vital to memory and learning. A key question is what causes the loss of the cells. As yet, scientists don't know the answer. Round plaques composed of a protein called amyloid are one of the hallmarks of Alzheimer's disease and increasing evidence suggests that amyloid causes the death of nerve cells.

In a new study, led by Claudio Soto, Ph.D., Research Assistant Professor of Neurology and Pathology at NYU School of Medicine, a custom-designed sequence of just five amino acids completely blocked the formation of amyloid in the brains of rats, destroyed already existing amyloid and prevented the death of nerve cells caused by amyloid in tissue cultures of human nerve cells. The findings are published in the July issue of the journal Nature Medicine.

"Whether or not amyloid formation directly causes Alzheimer's disease, it is a good target for therapy," says Dr. Soto. "We think that these findings open the way for a new therapeutic approach to treating Alzheimer's disease by preventing the deposition of senile plaques," says Dr. Soto. "We also believe that our compound may be useful in treating other diseases caused by defective protein folding, including prion disease and amyotrophic lateral sclerosis or Lou Gehrig's disease."

Amino acids hook together to form peptides and proteins. Amyloid plaque is deposited in the brain as sheets, explains Dr. Soto. These sheets, which may contain thousands of protein strings, form a shape called "beta-pleated." In order to continue forming the pleated sheets, the strings must be folded in a particular way that is abnormal. His team was able to prevent amyloid formation by custom-designing a rogue peptide that mimicked the region of the amyloid protein that regulates folding but contained certain amino acids unable to adopt the pleated form. They call the rogue a "beta-sheet breaker."

"We believe that in order for amyloid to be formed, the protein has to adopt this beta-sheet formation," says Dr. Soto. "The beta-sheet breaker peptide interferes with this process so amyloid plaque cannot form. And the breaker will also dissolve any amyloid that is already formed."

Although it isn't clear how the beta-sheet breaker works, Dr. Soto speculates that the short peptide may structurally modify the amyloid protein in solution, stabilizing the normal shape of the protein, which doesn't form plaque. Alternatively, the beta-sheet breaker may integrate itself into growing amyloid plaque, thwarting its growth.

Dr. Soto said that no other compound has ever been able to prevent amyloid formation in animal models of Alzheimer's disease. It is far too early to know whether the beta-sheet breaker could ever be used as a therapy in humans. Typically, a drug must be evaluated in animals before it reaches the earliest stages of human testing, a process that may take many years. Dr. Soto's compound is in the earliest stages of animal testing.

The beta-sheet breaker can cross the blood-brain barrier, according to ongoing animal studies by Dr. Soto. His team is also working with animal models of other diseases to assess if beta-sheet breaker peptides can be used to prevent abnormal folding of proteins implicated in conditions such as mad cow disease.


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Materials provided by New York University Medical Center And School Of Medicine. Note: Content may be edited for style and length.


Cite This Page:

New York University Medical Center And School Of Medicine. "A Synthetic Peptide Destroys Brain Plaque Implicated In Alzheimer's Disease." ScienceDaily. ScienceDaily, 2 July 1998. <www.sciencedaily.com/releases/1998/07/980702085718.htm>.
New York University Medical Center And School Of Medicine. (1998, July 2). A Synthetic Peptide Destroys Brain Plaque Implicated In Alzheimer's Disease. ScienceDaily. Retrieved March 28, 2024 from www.sciencedaily.com/releases/1998/07/980702085718.htm
New York University Medical Center And School Of Medicine. "A Synthetic Peptide Destroys Brain Plaque Implicated In Alzheimer's Disease." ScienceDaily. www.sciencedaily.com/releases/1998/07/980702085718.htm (accessed March 28, 2024).

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