Following destabilization of native protein folding by expanded polyglutamine domains, the aggregation of mutant huntingtin or ataxin-3 proceeds by nucleated growth polymerization into protein fibrils that structurally resemble amyloid fibrils and react with amyloid-specific histochemical dyes such as Congo Red or thioflavin. Analogous biophysical properties are observed for b-amyloid and a-synuclein fibrils associated with Alzheimer��s and Parkinson��s diseases, respectively. Amyloid fibrils are thought to be nucleated by monomers or globular oligomers of misfolded protein. In turn, fibrils may co-assemble into much larger insoluble protein aggregates that are resistant to proteolysis. While it is clear that protein misfolding can elicit cellular toxicity, whether fibrillar protein aggregates are Folinic acid calcium salt pentahydrate themselves toxic remains the subject of intense debate. On one hand, a growing body of evidence supports the “toxic soluble precursor” hypothesis in which end-stage protein fibrils are increasingly considered benign or even cytoprotective. In support of this hypothesis, small molecules that visibly stimulate inclusion-formation inside cells appear to be beneficial. However, contrasting studies have achieved Ginsenoside-F2 compelling cytoprotection by preventing fibrils and aggregates from forming at all. These competing hypotheses are not mutually exclusive given the growing diversity in “onpathway” and “off-pathway” protein folding conformations observed during amyloidogenesis. Conventional antibodies raised against amyloid conformations are known to cross-react with a wide variety of misfolded proteins, thereby illustrating that diverse amyloidogenic proteins share isomorphic features. However, these conformation-specific antibodies cannot be readily implemented inside living cells to investigate the conformational toxicity of intracellular amyloidogenic proteins such as huntingtin, a-synuclein, and ataxin-3 in situ. In an alternative approach, recombinant single-chain Fv antibodies, which preserve the binding specificities of monoclonal antibodies within the framework of a single small polypeptide, can be selected in vitro and expressed intracellularly as “intrabodies” to probe huntingtin and a-synuclein in living cells. By encoding the antigen-binding site of an immunoglobulin within the framework of a single nucleic acid coding sequence, scFvs are amenable .