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"It may be that in the neurodegenerative diseases characterized by fibrillization--which is essentially all of them--the fibrillization produces, as an alternative product, an amyloid pore. "We don't know whether the pore is formed on the pathway to the fibril or if there's a fork in the road somewhere and the protofibrils have a choice to either form a pore or form a fibril. We're trying to study that." Author and his team have taken a different approach than the ion-channel supporters in their attempt to identify the pathogenic species. They began by examining the effect on amyloid fibrillization of the mutations that cause inherited cases of Parkinson's and Alzheimer's. The group "found that the mutations promote the formation of amyloid protofibrils, and that led to the idea that the protofibrils, rather than the fibrils, could be pathogenic. But protofibrils can adopt many different sizes and shapes, so the researchers looked more closely to identify the conformation that was most harmful. "That's when we found that the mutations in both Parkinson's and Alzheimer's promote the formation of porelike structures." Author`s group has five recent and upcoming full papers in Biochemistry and the Journal of Molecular Biology that provide further information on pores. Authors demonstrated that "only the protofibrils are capable of disrupting membranes via a mechanism that is consistent with that mediated by a porelike structure. This proposed mechanism resembles the lethal pore-formation activity of toxins secreted by organisms such as Staphylococcus aureus, which causes food poisoning, and Bacillus anthracis, which causes anthrax.
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