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

Research output: Contribution to journalArticle

12 Scopus citations

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.

    Fingerprint

Keywords

  • α-synuclein
  • Atomic force microscopy
  • Huntingtin
  • Oligomer
  • Single chain variable domain antibody fragment
  • Toxicity

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this