| First Author | Miller TW | Year | 2005 |
| Journal | Neurobiol Dis | Volume | 19 |
| Issue | 1-2 | Pages | 47-56 |
| PubMed ID | 15837560 | Mgi Jnum | J:116299 |
| Mgi Id | MGI:3693872 | Doi | 10.1016/j.nbd.2004.11.003 |
| Citation | Miller TW, et al. (2005) A human single-chain Fv intrabody preferentially targets amino-terminal Huntingtin's fragments in striatal models of Huntington's disease. Neurobiol Dis 19(1-2):47-56 |
| abstractText | Amino-terminal fragments of huntingtin (htt) appear to result from proteolytic processing of the full-length protein in Huntington's disease (HD), and fragments containing pathological expansions of polyglutamine elicit toxicity in model systems. Such fragments are sequestered into insoluble aggregates, which may initially serve a cellular protective mechanism, while soluble fragments and/or oligomers may be a more acute toxic species. Agents which enhance mutant htt clearance have shown therapeutic potential in animal models of HD. Here, we present the first evidence of an htt-specific single-chain Fv intrabody (C4) that selectively targets the soluble fraction of amino-terminal htt fragments. Our findings suggest that the C4 intrabody binds weakly, but does not alter the levels of endogenous, full-length htt. C4 appears to decrease the steady-state levels of amino-terminal htt fragments by binding to non-aggregated, but not aggregated, htt species. Intrabodies may be used as potential curative agents, and as drug discovery tools, for HD and other misfolded protein disorders. |
