Scientists designed molecular inhibitors that could delay the onset of Alzheimer's disease and prevent the sexual transmission of HIV.
The researchers say the inhibitors target specific proteins associated with Alzheimer's disease and HIV to prevent them from forming amyloid fibres, the elongated chains of interlocking proteins that play a key role in more than two dozen degenerative and often fatal diseases.
Advertisement"By studying the structures of two key proteins that form amyloids, we were able to identify the small chain of amino acids responsible for amyloid fibre formation and engineer a 'molecular cap' that attaches to the end of the fibres to inhibit their growth," research leader David Eisenberg, director of the UCLA-Department of Energy Institute of Genomics and Proteomics and a Howard Hughes Medical Institute investigator, said.
"This research is an important first step toward the development of structure-based drugs designed against amyloid diseases," Eisenberg, who is a UCLA professor of chemistry, biochemistry and biological chemistry and a member of the California NanoSystems Institute at UCLA, said.
"Our results have opened up an avenue so that universities and industry can start creating therapeutics that could not have been produced 10 years ago," he stated.
Eisenberg and his research team found that of the entire tau protein, a small chain of just six amino acids - abbreviated VQIVYK - was responsible for the formation of amyloid fibres.
By studying the structure of the fibres using microcrystallography, a method developed at UCLA for this research, the team was able to use the fibres as a template to design an inhibitor that could "cap" the fibre and stop it from growing.
The introduction of the inhibitor into a tau protein solution completely prevented amyloid fibre formation, validating the idea that the structure-based design of therapeutics for amyloid diseases is a plausible option.
The study has been published online June 15 in the journal Nature and will be available in an upcoming print edition.
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