Huntington's and Parkinson's diseases are both neurodegenerative disorders caused at least in part by misfolding and aggregation of huntingtin (htt) and α-synuclein, respectively. Here we use a single chain antibody fragment (scFv) isolated against oligomeric α-synuclein to probe similarities and differences between the aggregation and toxic mechanisms of htt and α-synuclein. When incubated with htt, the scFv both blocks formation of and promotes dissociation of fibrillar aggregates, but stabilizes formation of cytotoxic oligomeric aggregates. Previous studies with monomeric α-synuclein showed the scFv prevented fibrillar aggregation, but blocked toxicity of oligomeric aggregates. These divergent effects suggest the toxic mechanisms of oligomeric aggregates differ among amyloidogenic protein species.
- Atomic force microscopy
- Single chain variable domain antibody fragment
ASJC Scopus subject areas
- Molecular Biology