| First Author | Koyama S | Year | 2006 |
| Journal | Biochem Biophys Res Commun | Volume | 343 |
| Issue | 3 | Pages | 719-30 |
| PubMed ID | 16563356 | Mgi Jnum | J:107550 |
| Mgi Id | MGI:3621402 | Doi | 10.1016/j.bbrc.2006.02.170 |
| Citation | Koyama S, et al. (2006) Alteration of familial ALS-linked mutant SOD1 solubility with disease progression: Its modulation by the proteasome and Hsp70. Biochem Biophys Res Commun 343(3):719-30 |
| abstractText | Accumulation of misfolded Cu/Zn superoxide dismutase (SOD1) occurs in patients with a subgroup of familial amyotrophic lateral sclerosis (fALS). To identify the conversion of SOD1 from a normally soluble form to insoluble aggregates, we investigated the change of SOD1 solubility with aging in fALS-linked H46R SOD1 transgenic mice. Mutant SOD1 specifically altered to insoluble forms, which were sequentially separated into Triton X-100-insoluble/sodium dodecyl sulfate (SDS)-soluble and SDS-insoluble/formic acid-soluble species. In spinal cords, the levels of SDS-dissociable soluble SOD1 monomers and SDS-stable soluble dimers were significantly elevated before motor dysfunction onset. In COS-7 cells expressing H46R SOD1, treatment with proteasome inhibitors recapitulated the alteration of SOD1 solubility in transgenic mice. In contrast, overexpression of Hsp70 reduced accumulation of mutant-specific insoluble SOD1. SDS-soluble low molecular weight species of H46R SOD1 may appear as early misfolded intermediates when their concentration exceeds the capacity of the proteasome and molecular chaperones. |
