Conformational targeting of fibrillar polyglutamine proteins in live cells escalates aggregation and cytotoxicity.

ABSTRACT:

Background

Misfolding- and aggregation-prone proteins underlying Parkinson's, Huntington's and Machado-Joseph diseases, namely alpha-synuclein, huntingtin, and ataxin-3 respectively, adopt numerous intracellular conformations during pathogenesis, including globular intermediates and insoluble amyloid-like fibrils. Such conformational diversity has complicated research into amyloid-associated intracellular dysfunction and neurodegeneration. To this end, recombinant single-chain Fv antibodies (scFvs) are compelling molecular tools that can be selected against specific protein conformations, and expressed inside cells as intrabodies, for investigative and therapeutic purposes.

Methodology/principal findings

Using atomic force microscopy (AFM) and live-cell fluorescence microsco

SUBMITTER: Kvam E 

PROVIDER: S-EPMC2683928 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature