| SUBJECT |
Authors 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." shows images of the amyloid pores. The large size of the holes seen in these electron microscopy images "suggests that the amyloid proteins are more likely to form rather unspecific pores than channels that are specific for certain ions. Author`s group has five recent and upcoming full papers in Biochemistry and the Journal of Molecular Biology that provide further information on pores. 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. Atomic force microscopy images of the -synuclein amyloid pores in membranes provide additional evidence. Authors have shown that amyloid fibrils are unable to form holes in vesicles
|