New York, October 28 (IBNS): One of the hallmarks of Alzheimer's disease, a debilitating disorder characterized by memory deficits and general cognitive decline, is the accumulation of a protein called b-amyloid in the brain. These proteins form "plaques" and bind to unique proteins on the surface of brain cells called receptors that cause widespread cell death.
Now, UCLA researchers have discovered a drug that prevents the binding of b-amyloid plaques to brain cells to extensive cell death. The study was published in the journal Nature Chemistry.
Dr. Lin Jiang, Assistant Professor of Neurology, in collaboration with David Eisenberg, Professor of Chemistry and Biochemistry and Biochemistry at UCLA, identified the plaque binding site of b-amyloid at its receptor by determining its three-dimensional structure. The knowledge about this interaction is a critical first step on the way to a drug to prevent the interaction between the toxic proteins and the brain cells. Jiang and his team then used computer software to assist them in drug selection.
"We were looking for a molecule that can block the receptor like a shield, preventing b-amyloid from binding and killing brain cells," said Jiang
To identify molecular candidates for blocking the To find interaction between b-amyloid and brain cells, Jiang and his colleagues searched a library of more than 32,000 molecules. This list included medicinal products that are authorized for human use, are currently in clinical trials or are found in nature. This meant that many properties 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 the extent of cell death between the groups. ALI6 treatment almost completely prevented b-amyloid-induced cell death, suggesting that the drug could potentially be used to treat Alzheimer's disease.
ALI6 is a promising candidate. Not only is it non-toxic, it can also pass from the bloodstream to the brain, a crucial property for any drug that targets the treatment of central nervous system disorders such as Alzheimer's disease. In addition, ALI6 offers a distinct advantage over other treatments.
"At present, many drugs are designed to prevent the accumulation and formation of b-amyloid proteins, as this is the dangerous form of the protein," said Jiang. "However, if one person is diagnosed with Alzheimer's, many of the b-amyloid plaques have already formed, so the window of opportunity for treatment is already closing."
Alzheimer's disease is the sixth most common 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 animal studies before human studies could begin.
Other authors of the study include: Qin Cao, Woo Shik Shin, Henry Chan, Celine Vuong, Bethany Dubois, Lin Li, Kevin Murray, Michael Sawaya, Juli Feigon, and Douglas Black, all at UCLA
This The study was funded by the Turken Research Award and the Jiang Department's Recruitment Department; and grants from the National Institutes of Health, Department of Energy, and Howard Hughes Medical Institute to Eisenberg
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