Anti-oligomeric single chain variable domain antibody differentially affects huntingtin and alpha-synuclein aggregates.
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.
Nannenga
Brent L
BL
Department of Chemical Engineering, Arizona State University, Tempe, AZ 85287, USA.
Zameer
Andleeb
A
Sierks
Michael R
MR
D001704:Biopolymers / Q000276:immunology*; D006801:Humans; D000071058:Huntingtin Protein; D007128:Immunoglobulin Fragments / Q000276:immunology*; D018625:Microscopy, Atomic Force; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000276:immunology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000276:immunology*; D051844:alpha-Synuclein / Q000737:chemistry / Q000276:immunology*
D001704:Biopolymers; C086055:HTT protein, human; D000071058:Huntingtin Protein; D007128:Immunoglobulin Fragments; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051844:alpha-Synuclein