| First Author | Lee JK | Year | 2015 |
| Journal | Neurobiol Dis | Volume | 80 |
| Pages | 63-9 | PubMed ID | 26002422 |
| Mgi Jnum | J:223405 | Mgi Id | MGI:5648778 |
| Doi | 10.1016/j.nbd.2015.05.009 | Citation | Lee JK, et al. (2015) Iron accumulation promotes TACE-mediated TNF-alpha secretion and neurodegeneration in a mouse model of ALS. Neurobiol Dis 80:63-9 |
| abstractText | Oxidative stress contributes to degeneration of motor neurons in patients with amyotrophic lateral sclerosis (ALS) as well as transgenic mice overexpressing ALS-associated human superoxide dismutase 1 (SOD1) mutants. However, the molecular mechanism by which the ALS-linked SOD1 mutants including SOD1(G93A) induce oxidative stress remains unclear. Here, we show that iron was accumulated in ventral motor neurons from SOD1(G93A)-transgenic mice even at 4 weeks of age, subsequently inducing oxidative stress. Iron chelation with deferoxamine mesylate delayed disease onset and extended lifespan of SOD1(G93A) mice. Furthermore, SOD1(G93A)-induced iron accumulation mediated the increase in the enzymatic activity of TNF-alpha converting enzyme (TACE), leading to secretion of TNF-alpha at least in part through iron-dependent oxidative stress. Our findings suggest iron as a key determinant of early motor neuron degeneration as well as proinflammatory responses at symptomatic stage in SOD1(G93A) mice. |
