Abstract
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.
Original language | English (US) |
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Pages (from-to) | 517-522 |
Number of pages | 6 |
Journal | FEBS Letters |
Volume | 582 |
Issue number | 4 |
DOIs | |
State | Published - Feb 20 2008 |
Keywords
- Atomic force microscopy
- Huntingtin
- Oligomer
- Single chain variable domain antibody fragment
- Toxicity
- α-synuclein
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology