Now, UCLA researchers have discovered a drug that blocks b-amyloid plaques from attaching to brain cells, preventing extensive cell death.…
Now, UCLA researchers have discovered a drug that blocks b-amyloid plaques from attaching to brain cells, preventing extensive cell death. The study was published in the journal Nature Chemistry.
Dr. Lin Jiang, Assistant Professor of Neurology, working with David Eisenberg, Professor of Chemistry and Biochemistry and Biological Chemistry at UCLA, identified the binding site for b-amyloid to its receptor by determining the three-dimensional structure. Knowledge of this interaction is a critical first step towards finding a drug to prevent interaction between the toxic proteins and brain cells. Jiang and his team then used computer software to help them in the choice of drug selection.
“We were looking for a molecule that could block the receptor as a shield, preventing b-amyloid from tying and killing brain cells,” Jiang said.
To find molecular candidates to block the b-amyloid / brain cell interaction, Jiang and colleagues sought a library containing more than 32,000 molecules. This list contained drugs that are approved for human use, are currently in clinical trials or are naturally occurring. This meant that many properties of drug candidates were already known and they were safe for human use.
From this list of molecules, a drug, ALI6, showed promising results in cell-based experiments.
Jiang and his team cultured mice cells and exposed them to the toxic B-amyloid proteins, then treated some cells with ALI6 and compared levels of cell death between groups. ALI6 treatment almost completely prevented cell death caused by b-amyloid, suggesting that the drug could ultimately be investigated to treat Alzheimer’s disease.
ALI6 is a promising candidate. Not only is it poison-free but it can also go from the bloodstream to the brain, a critical feature of any drug aimed at treating central nervous system disorders such as Alzheimer’s disease. In addition, ALI6 has a distinct advantage over other treatments.
“Currently, many drugs are aimed at preventing the b-amyloid proteins from accumulating and forming in plaques because it is the dangerous form of the protein,” said Jiang. “However, when a person is diagnosed with Alzheimer’s disease, many of the b-amyloid plaques have already been formed, so that the time window for treatment is already completed.”
Alzheimer’s disease is the sixth leading cause of death in the United States, with an estimated 5.5 million people currently living with the disease.
The results of this study would have to be confirmed in further experiments in animals before human studies could begin.
The study’s other authors include: Qin Cao, Woo Shik Shin, Henry Chan, Celine Vuong, Bethany Dubois, Binsen Li, Kevin Murray, Michael Sawaya, July Feigon and Douglas Black, all UCLA.
This study was funded by the Turken Research Award and department recruiting agent for Jiang; as well as contributions from the National Institute of Health, the Department of Energy and the Howard Hughes Medical Institute to Eisenberg.
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