UCLA researchers have discovered a drug that blocks b-amyloid plaques from attaching to brain cells, preventing the extensive cell death. The study was published in the journal Nature Chemistry.
Dr. Lin Jiang, assistant professor of neurology, working with David Eisenberg, a professor of chemistry and biochemistry and of biological chemistry at UCLA, identified the plaque binding site of b-amyloid to its receptor by determining the three-dimensional structure. Knowledge of this interaction is a critical first step toward finding a drug to prevent the interaction between the toxic proteins and brain cells. Jiang and his team used computer software to assist them in the drug selection process.
The scientists were searching for a molecule that could block the receptor like a shield, preventing b-amyloid from binding to and killing brain cells. In order to find molecular candidates to block the b-amyloid/brain cell interaction, they searched a library containing more than 32,000 molecules. This list contained drugs that are approved for human use, are currently in clinical trial, or are naturally occurring. This meant that many characteristics of the drug candidates were already known and they were safe for human use. From this list of molecules, one drug, ALI6, showed promising results in cell-based experiments.
Jiang and his team cultured mouse brain 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 the cell death caused by b-amyloid, suggesting that the drug could eventually be explored to treat Alzheimer’s disease.
ALI6 is a promising candidate. Not only is it non-toxic but it can also move from the bloodstream to the brain, a critical trait for any drug aimed at treating central nervous system disorders such as Alzheimer’s disease. In addition, ALI6 offers a distinct advantage over other treatments.
The findings of this study would need to be confirmed in further tests in animals before human studies could begin.
Source: UCL Newsroom | October 22, 2018