| First Author | Riehm JJ | Year | 2018 |
| Journal | Neurobiol Dis | Volume | 115 |
| Pages | 115-126 | PubMed ID | 29627580 |
| Mgi Jnum | J:268556 | Mgi Id | MGI:6267153 |
| Doi | 10.1016/j.nbd.2018.03.014 | Citation | Riehm JJ, et al. (2018) Poloxamer 188 decreases membrane toxicity of mutant SOD1 and ameliorates pathology observed in SOD1 mouse model for ALS. Neurobiol Dis 115:115-126 |
| abstractText | Here we report a gain in function for mutant (mt) superoxide dismutase I (SOD1), a cause of familial amyotrophic lateral sclerosis (FALS), wherein small soluble oligomers of mtSOD1 acquire a membrane toxicity. Phosphatidylglycerol (PG) lipid domains are selectively targeted, which could result in membrane damage or "toxic channels" becoming active in the bilayer. This PG-selective SOD1-mediated membrane toxicity is largely reversible in vitro by a widely-available FDA-approved surfactant and membrane-stabilizer P188. Treatment of G93ASOD1 transgenic mice with P188 significantly delayed symptoms onset, extended survival and decreased motoneuron death. The use of P188 or an analogue, which targets mtSOD1 misfolding-induced membrane toxicity, may provide a new direction for ALS treatment. |
