摘要
It is well reported that cellular ferritin reduces the intracellular oxidative stress by sequestering excess ferrous ions,preventing them from participating in Fenton reactions that generate damaging harmful reactive oxygen species(ROS).Here we show a novel property of the native human ferritin H subunit nanoparticles(HFn NPs),which can function as catalase by effectively decomposing H_(2)O_(2) into H_(2)O and O_(2) in vivo that plays an important role in maintaining cellular redox homeostasis and in disease resistance.It was revealed that the catalase-like activity of HFn can be greatly increased by loading iron ions within the cavity of HFn nanocage.Moreover,HFn and iron-loaded HFn(HFn-Fe)can largely eliminate the oxidative damage caused by excess H_(2)O_(2) to live cells or Caenorhabditis elegans(C.elegans).Feeding HFn or HFn-Fe to C.elegans A30P Parkinson’s disease(PD)model significantly ameliorated theα-synuclein toxicity and alleviated the dendrite dysfunction in C.elegans PD models by substantively scavenging the in vivo H_(2)O_(2).This work demonstrates that the revealed novel catalase-like property of native HFn and HFn-Fe NPs may play an important role in maintaining cellular redox homeostasis and can be used as an effective therapeutic strategy against neurodegenerative diseases caused by redox dysregulation.
基金
This work was supported by the National Key R&D Program of China(No.2022YFA1205801)
National Natural Science Foundation of China(Nos.T2225026,82172087,82071308,and 82404099)
Peking University Third Hospital Clinical Key Project(Nos.BYSYZD2023041 and BYSYRCYJ2023004)
Beijing Institute of Technology Research Fund Program for Young Scholars,and Outstanding Young Talent Project of Capital Medical University.
