Anti-oligomeric single chain variable domain antibody differentially affects huntingtin and alpha-synuclein aggregates

作者：Nannenga Brent L; Zameer Andleeb; Sierks Michael R^*

来源：FEBS Letters, 2008, 582(4): 517-522.

DOI：10.1016/j.febslet.2008.01.014

• single chain variable domain antibody fragment
• atomic force microscopy
• oligomer
• huntingtin
• alpha-synuclein
• toxicity

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.

• 出版日期2008-2-20