Proteins implicated in neurological conformational diseases contain substantial amounts
of “intrinsic disorder”. These native monomeric functional states may transit into some oligomeric
states that have high β-sheet contents and seed the formation of insoluble amyloid fibrils. The prevailing
view is that these “toxic” oligomers should be targeted for drug development. Here, an overview
of the diseases was presented, within the general framework of the oligomerization of intrinsically
disordered proteins. These systems pose some specific challenges to structural studies: the toxic
oligomers are transient, low in concentration, and often need to be studied in a heterogeneous environment.
Nevertheless, there have been much exciting progress as a result of the creative use of experimental
techniques, a selection of these were outlined.
Keywords: Misfolding, neurodegeneration, intrinsically disordered proteins, IDP, oligomerization, aggregation.
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