Molecular structure of amyloid fibrils controls the relationship between fibrillar size and toxicity.

ABSTRACT:

Background

According to the prevailing view, soluble oligomers or small fibrillar fragments are considered to be the most toxic species in prion diseases. To test this hypothesis, two conformationally different amyloid states were produced from the same highly pure recombinant full-length prion protein (rPrP). The cytotoxic potential of intact fibrils and fibrillar fragments generated by sonication from these two states was tested using cultured cells.

Methodology/principal findings

For one amyloid state, fibril fragmentation was found to enhance its cytotoxic potential, whereas for another amyloid state formed within the same amino acid sequence, the fragmented fibrils were found to be substantially less toxic than the intact fibrils. Consistent with the previous studies, t

SUBMITTER: Lee YJ 

PROVIDER: S-EPMC3098877 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature