Scientists have previously suggested that mature fibrils of the amyloid polypeptide protein the key component of the islet deposits are toxic to cells in the pancreas that produce insulin, attacking through tiny holes in the cell membrane. Gazit and his colleagues, graduate student Yair Porat and Sofiya Kolusheva and Raz Jelinek from Ben Gurion University, studied the interactions between the protein and cell membrane. They discovered that smaller structures formed prior to the mature fibrils, called protofibrils, are more likely to get through the membrane, and may therefore be the more toxic species.
In the past few years, other scientists have noticed the effects of protofibrils while studying Alzheimer's and Parkinson's, but the notion that they may be the main culprits is fairly new. Earlier this summer in another Biochemistry paper, Peter Lansbury of Harvard University suggested a possible therapeutic strategy for Parkinson's based on stopping the formation of protofibrils.
"A very interesting point is the striking similarity between these assemblies and the structures observed in the cases of Alzehimer's disease and Parkinson's disease," Gazit says. The new study offers solid experimental evidence of the phenomenon in type II diabetes, and demonstrates a common thread among the three diseases.
The majority of research continues to focus on mature fibrils, but this could prove to be dangerous if the new protofibril mechanism is correct, according to Gazit. Breaking up the large amyloid deposits may actually increase the number of protofi
Contact: Michael Bernstein
American Chemical Society