关键词：蛋白质；脑脊液；铁；脂质体；运动神经元
摘 要：Iron accumulation and deposition have been reported in patients with amyotrophic lateral sclerosis (ALS). Previous work in mutant SOD1 mice mouse models of ALS have indicated that iron chelation with a chemical agent extends lifespan. Therefore, we propose the use of apo-ferritin, the iron-storage protein ferritin that is iron-poor, as a natural ionophore to sequester excess iron and redistribute it. The overall hypothesis is that infusion of apo- ferritin protein into the brain will provide neuroprotection by limiting the availability of excess iron to catalyze free-radical production. The most significant findings from this project are: (1) Infusion of artificial cerebrospinal fluid (aCSF) containing nutrients, including H-ferritin, increases lifespan and delays onset of disease in SOD1G93A mice; (2) This effect is not achieved by infusion of saline, suggesting that there is more than just a mechanical benefit to increasing flow of CSF (3) In an accelerated disease model of ALS where mice carry both the HFEH67D allelic variant, present in 30% of ALS patients, and the SOD1G93A mutation, infusion of aCSF with or without H-ferritin is not beneficial. The high rate of oxidative stress in these animals may be too great for an infusion strategy; (4) Infusion of H- ferritin protein encapsulated in liposomes is even more effective at delaying onset and extending lifespan than H-ferritin protein directly infused. The potential clinical significance of this work is that increasing turn-over of cerebrospinal fluid, and providing H-ferritin in a manner that may be more likely to be taken up by cells, appear to be viable therapeutic options for ALS patients.