Researchers at the University of Leeds have outlined how antibiotic resistance could contribute to a cure for diseases such as type 2 diabetes and Alzheimer’s disease.
Type 2 diabetes, Alzheimer’s and Parkinson’s are all examples of “amyloid diseases”. Unlike most other disease, which are linked to a single enzyme or receptor, amyloid diseases are related to numerous proteins that have stuck together. This makes them particularly difficult to treat, and, currently, impossible to cure.
In this study, researchers from the Astbury Centre for Structural Molecular Biology at the University of Leeds found that antibiotic resistance could be used to find chemicals that can stop the formation of amyloids in the first place.
Antibiotics and amyloid disease
“Until now, we haven’t had effective ways to identify drugs to combat amyloid formatio,” said Professor Sheena Radford, FRS Director of the Astbury Centre for Structural Molecular Biology at the University of Leeds. “Amyloid-prone proteins often don’t have a clearly defined structure, which makes it very difficult to identify areas to target with drugs.
“Also, because amyloid-causing proteins have a tendency to stick together, they can be very hard to study in the lab. This study shows a way of getting around these problems by grafting amyloid-prone sequences into enzymes which break down antibiotics.”
The researchers added amyloid-prone sequences to beta-lactamase enzymes, which destroy antibiotics. However, because of the amyloid-causing sequences, the beta-lactamase enzymes were unable to destroy the antibiotics, so the bacteria was able to grow.
Dr. Janet Saunders, a researcher on the study, said: “In our research, an old enemy – anti-bacterial resistance – turns out to be our friend. When we see bacterial growth, we know we have chemicals that are obstructing amyloid formation.”
“You can screen thousands of compounds by putting them through this test”
Although one such chemical identified by the researchers – L-dopamine – is closely linked to type 2 diabetes, perhaps the most important thing about the findings is how quickly and efficiently it can be used to screen different proteins associated with amyloid disease.
“If you can insert a protein sequence into beta-lactamase, you are likely to be able to use this technique as a screen for chemicals capable of inhibiting its aggregatio,” said co-author Dr. David Brockwell, Associate Professor in the University’s School of Molecular and Cellular Biology. “You can screen thousands of compounds by putting them through this test.”
Professor Radford stressed that screening amyloid proteins is only part of the battle. It is a first step in a long process of discovering a cure for amyloid diseases.
Professor Radford said: “It is important to stress that an efficient screen is only one step in the journey toward drug discovery. The power of our study is that it provides the first step on this path by showing us the type of molecules we should be looking at to inhibit a particular disease-causing protein.”
The findings are published in Nature Chemical Biology.

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