title: Prevention of motor neuron degeneration by novel iron chelators in SOD1(G93A) transgenic mice of amyotrophic lateral sclerosis.
abstract: BACKGROUND
  The causes of amyotrophic lateral sclerosis (ALS) are largely unknown. Oxidative stress is considered to play a major role in motor neuron degeneration associated with iron homeostasis disturbance.
  
  
  OBJECTIVE
  Iron chelation treatment might be a potential therapeutic approach on the basis of its ability to reduce the oxygen free radical generation caused by iron accumulation.
  
  
  RESULTS
  In the present study, we applied the brain-permeable iron chelators VK-28 and M30 in a G93A mutant superoxide dismutase 1 transgenic (SOD1(G93A)) mouse model of ALS and found that VK-28 and M30 significantly delayed disease onset, extended the life span and reduced spinal cord motor neuron loss. Furthermore, we documented that both iron chelators significantly attenuated the elevated iron level and transferrin receptor expression, decreased oxygen free radicals and suppressed microglial and astrocytic activation in the spinal cords of the SOD1(G93A) mice. Moreover, we demonstrated that both iron chelators were able to decrease TDP-43 protein aggregation and the proapoptotic molecule Bax, and to enhance antiapoptotic protein Bcl-2 expression, in the ALS mice.
  
  
  CONCLUSIONS
  These results provide evidence that iron is involved in the pathogenesis of ALS and iron chelation therapy may have the potential for the prevention and treatment of ALS.
authors.affiliation: Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Zhang
authors.forename: Sheng
authors.initials: S
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Sufang
authors.initials: S
authors.lastname: Zhang
authors.forename: Moussa
authors.initials: M
authors.lastname: Youdium
authors.forename: Weidong
authors.initials: W
authors.lastname: Le
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control; D000818:Animals; D007502:Iron Chelating Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D009410:Nerve Degeneration / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control*; D018384:Oxidative Stress / Q000235:genetics; D011897:Random Allocation; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
chemical_list: D007502:Iron Chelating Agents; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase