Researchers create molecule that blocks pathway leading to Alzheimer's disease

April 30, 2012

UC Davis researchers have found novel compounds that disrupt the formation of amyloid, the clumps of protein in the brains of people with Alzheimer's disease believed to be important in causing the disease's characteristic mental decline. The so-called "spin-labeled fluorene compounds" are an important new target for researchers and physicians focused on diagnosing, treating and studying the disease.

The study, published today in the online journal PLoS ONE, is entitled "The influence of spin-labeled fluorene compounds on the assembly and of the Aβ peptide."

"We have found these small molecules to have significant beneficial effects on cultured neurons, from protecting against toxic compounds that form in neurons to reducing inflammatory factors," said John C. Voss, professor of biochemistry and molecular medicine at the UC Davis School of Medicine and the principal investigator of the study. "As a result, they have great potential as a therapeutic agent to prevent or delay injury in individuals in the earliest stages of Alzheimer's disease, before significant damage to the occurs."

Amyloid is an accumulation of proteins and peptides that are otherwise found naturally in the body. One component of amyloid − the amyloid beta (Aβ) peptide − is believed to be primarily responsible for destroying neurons in the brain. Fluorene compounds, which are small three-ringed molecules, originally were developed as imaging agents to detect amyloid with PET imaging. In addition to being excellent for detecting amyloid, fluorenes bind and destabilize Aβ peptide and thereby reduce amyloid formation, according to previous findings in mice by Lee-Way Jin, another study author and associate professor in the UC Davis MIND Institute and Department of Medical Pathology and Laboratory Medicine.

The current research studied the effects of fluorene compounds by attaching a special molecule to make their activity evident using electron paramagnetic resonance (EPR) spectroscopy. This technology allows researchers to observe very specific activities of molecules of interest because biological tissues do not emit signals detectable by EPR. Since Voss was interested in the activity of fluorenes, he added a nitroxide "spin label," a chemical species with a unique signal that can be measured by EPR.

The group found that spin-labeled compounds disrupted Aβ peptide formation even more effectively than did non-labeled fluorenes. In addition, the antioxidant properties of the nitroxide, which scavenge reactive oxygen species known to damage neurons and increase inflammation, significantly contributed to the protective effects on neurons.

"The spin-labeled fluorenes demonstrated a number of extremely important qualities: They are excellent for detecting amyloid in imaging studies, they disrupt Aβ formation, and they reduce inflammation," said Voss. "This makes them potentially useful in the areas of research, diagnostics and treatment of Alzheimer's disease."

Alzheimer's disease is the most common form of dementia and affects some 5 million Americans. Current medications used to fight the disease usually have only small and temporary benefits, and commonly have many side effects.

A major obstacle in developing Alzheimer's disease therapy is that most molecules will not cross the blood-brain barrier, so that potential treatments given orally or injected into the bloodstream cannot enter the brain where they are needed. Fluorene compounds are small molecules that have been shown to penetrate the brain well.

"We have brought together expertise from diverse fields to get to this point, and what was once a side interest has become a major focus," said Voss. "We are very excited and hopeful that these unique compounds can become extremely important."

Voss' group next plans to study the safety of spin-labeled fluorene compounds as well as their efficacy for treating models of Alzheimer's disease in small animals.

Explore further: Advances in research into Alzheimer's disease

Related Stories

Advances in research into Alzheimer's disease

July 9, 2011
Advances in research into Alzheimer's disease: transporter proteins at the blood CSF barrier and vitamin D may help prevent amyloid β build up in the brain

Overlooked peptide reveals clues to causes of Alzheimer's disease

July 3, 2011
Researchers at the RIKEN Brain Science Institute (BSI) and their collaborators have shed light on the function of a little-studied amyloid peptide in promoting Alzheimer's disease (AD). Their surprising findings reveal that ...

Scientists study link between amyloid beta peptide levels and Alzheimer's disease

March 20, 2012
The effects of the bacterial endotoxin lipopolysaccharide (LPS) has been found to elevate amyloid beta (Aβ) peptide levels in the brain, leading to short-term deficits in learning.

Recommended for you

Lifestyle changes to stave off Alzheimer's? Hints, no proof

July 20, 2017
There are no proven ways to stave off Alzheimer's, but a new report raises the prospect that avoiding nine key risks starting in childhood just might delay or even prevent about a third of dementia cases around the world.

Blood test identifies key Alzheimer's marker

July 19, 2017
A new study led by researchers at Washington University School of Medicine in St. Louis suggests that measures of amyloid beta in the blood have the potential to help identify people with altered levels of amyloid in their ...

Steering an enzyme's 'scissors' shows potential for stopping Alzheimer's disease

July 19, 2017
The old real estate adage about "location, location, location" might also apply to the biochemical genesis of Alzheimer's disease, according to new research from the University of British Columbia.

Brain scans may change care for some people with memory loss

July 19, 2017
Does it really take an expensive brain scan to diagnose Alzheimer's? Not everybody needs one but new research suggests that for a surprising number of patients whose memory problems are hard to pin down, PET scans may lead ...

Can poor sleep boost odds for Alzheimer's?

July 18, 2017
(HealthDay)— Breathing problems during sleep may signal an increased risk for Alzheimer's disease, a trio of studies suggests.

Hearing is believing: Speech may be a clue to mental decline

July 17, 2017
Your speech may, um, help reveal if you're uh ... developing thinking problems. More pauses, filler words and other verbal changes might be an early sign of mental decline, which can lead to Alzheimer's disease, a study suggests.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.