Antibiotic resistance could hold key for treating amyloid diseases
14 Jan 2016 by Evoluted New Media
Researchers have discovered a method of using antibiotic resistance to find chemicals that stop amyloids – misfolded proteins - forming.
Researchers have discovered a method of using antibiotic resistance to find chemicals that stop amyloids – misfolded proteins - forming.
Amyloid diseases include Parkinson’s, Alzheimer’s and Type 2 diabetes.
Professor Sheena Radford, at the University of Leeds, said: “Until now, we haven't had effective ways to identify drugs to combat amyloid formation. 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."
Researchers attached amyloid-prone sequences from target proteins to antibiotic degrading beta-lactamase enzymes. The bacteria with the modified enzymes were placed in petri dishes with the antibiotic.
Usually, the beta-lactamase would render the antibiotic inert, allowing bacteria to grow. The scientist found the amyloid-prone sequences prevented the enzymes from stopping bacterial growth.
Different chemicals were added to see if they inhibited the amyloid-causing sequence, which allowed the beta-lactamase to interact with the bacteria, resulting in bacterial growth.
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."
L-dopamine was identified as a chemical that blocks amyloid deposits forming from type 2 diabetes associated sequences.
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 study was published in Nature Chemical Biology.
