Toxic species in XXXX : Oligomers or mature fibrils.

@entity137 @entity26548 @entity191 @entity179 @entity74 @entity6960 @entity195
Protein aggregation is the hallmark of several @entity179 . These @entity6960 (fibrillization) disorders are also known as @entity74 . The mechanism of @entity6960 involves conformation switch of the native protein, oligomer formation leading to protofibrils and finally mature fibrils. Mature fibrils have long been considered as the cause of disease pathogenesis; however, recent evidences suggest oligomeric intermediates formed during fibrillization to be toxic. In this review, we have tried to address the ongoing debate for these toxic amyloid species. We did an extensive literature search and collated information from Pubmed (http://www.ncbi.nlm.nih. @entity26548 ) and Google search using various permutations and combinations of the following keywords: @entity179 , @entity6960 , fibrils, oligomers, @entity137 , @entity195 , @entity191 . We describe different instances showing the @entity137 of mature fibrils as well as oligomers in @entity195 and @entity191 . Distinct structural framework and morphology of amyloid oligomers suggests difference in toxic effect between oligomers and fibrils. We highlight the difference in structure and proposed @entity137 pathways for fibrils and oligomers. We also highlight the evidences indicating that intermediary oligomeric species can act as potential diagnostic biomarker. Since the formation of these toxic species follow a common structural switch among @entity74 , the @entity6960 events can be targeted for developing broad-range therapeutics. The therapeutic trials based on the understanding of different protein conformers (monomers, oligomers, protofibrils and fibrils) in amyloid cascade are also described.
