Anti-oligomeric single chain variable domain antibody differentially affects huntingtin and alpha-synuclein aggregates |
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Authors: | Nannenga Brent L Zameer Andleeb Sierks Michael R |
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Institution: | Department of Chemical Engineering, Arizona State University, Tempe, AZ 85287, USA. |
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Abstract: | Huntington's and Parkinson's diseases are both neurodegenerative disorders caused at least in part by misfolding and aggregation of huntingtin (htt) and alpha-synuclein, respectively. Here we use a single chain antibody fragment (scFv) isolated against oligomeric alpha-synuclein to probe similarities and differences between the aggregation and toxic mechanisms of htt and alpha-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 alpha-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. |
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Keywords: | scFv single chain variable domain antibody fragment AFM atomic force microscopy LDH lactate dehydrogenase HD Huntington’s disease SDS-PAGE sodium dodecylsulfate-polyacrylamide gel electrophoresis ThS Thioflavine S |
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