A recently developed technique for screening recombinant scFv libraries against amyloidogenic protein morphologies has identified several human conformation-specific scFvs against oligomeric and fibrillar forms of a-synuclein. Here, we demonstrate that one such scFv antibody selected against fibrillar a-synuclein targets isomorphic conformations of mutant huntingtin and ataxin-3 and enhances the aggregation propensity of these polyglutamine proteins in striatal cells. Using intrabodies as kinetic tools for controlling amyloidogenesis, we show that accelerating polyglutamine aggregation is not cytoprotective but rather aggravates intracellular dysfunction and cell death. These findings validate the importance of aggregation kinetics in modulating the severity of polyglutamine-mediated neuronal dysfunction. Drawing from evidence that fibrils of diverse amyloidogenic proteins possess common structural epitopes, we reasoned that scFv-6E may function as a conformational sensor for other fibril-forming proteins such as polyglutamine proteins. Therefore, we tested scFv-6E in cellular models of polyglutamine disease using either human ataxin-3 or a pathologic huntingtin fragment encoded by the first exon of the Huntingtin gene, both of which form filamentous protein Ginsenoside-F5 aggregates dependent on polyglutamine tract length. Through live-cell Folinic acid calcium salt pentahydrate microscopy, we confirmed that green fluorescent protein tagged versions of these misfolding-prone proteins formed intracellular aggregates in immortalized rat striatal progenitor cells with similar characteristics as widely documented in the literature. ST14A cells were chosen for this study because these neuronal cells share features with medium-spiny neurons, which are pre-disposed to HD neuropathology and affected in models of MJD. We included in our transfections a nuclear localization signal -tagged monomeric red fluorescent protein to label nuclei. Aside from this general purpose, NLSmRFP is a convenient marker for monitoring cellular stress in live cells, as its mislocalization to the cytoplasm is indicative of nuclear import collapse. As illustrated in Figure 1A, GFP-labeled mutant httex1, containing an expanded polyglutamine repeat associated with juvenile HD onset, rapidly formed cytoplasmic and perinuclear aggregates in ST14A cells after 48 hours, whereas httex1 containing a non-amyloidogenic polyglutamine repeat remained completely diffuse.