Iron deposition in Parkinson’s disease(PD)is a potential disease-modifying target.We previously showed that supplementation of the iron-exporter,ceruloplasmin,selectively corrected nigral iron elevation in the 1-meth...Iron deposition in Parkinson’s disease(PD)is a potential disease-modifying target.We previously showed that supplementation of the iron-exporter,ceruloplasmin,selectively corrected nigral iron elevation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)model.Ceruloplasmin delivers iron to transferrin(Tf),the extracellular iron-transporting protein.We show that Tf protein levels are decreased in the nigra of post-mortem PD brains compared with controls(−35%;n=10 each).Because Tf traffics iron away from iron-replete tissues,we hypothesized that Tf supplementation could selectively facilitate iron export from the nigra in PD.In cultured neurons,Tf treatment corrected iron accumulation,and subcutaneous Tf to mice ameliorated iron accumulation and motor deficits in the MPTP model of PD.Although these data support a role for Tf in the disease mechanism for PD,and its potential use for correcting disorders of iron overload,Tf therapy also caused systemic iron depletion,which could limit its application for PD.展开更多
基金This work was supported by funds from the Australian Research Council,the Australian National Health&Medical Research Council(GNT1100441 and GNT1044542)the CRC for Mental Health and Operational Infrastructure Support Victorian State Government。
文摘Iron deposition in Parkinson’s disease(PD)is a potential disease-modifying target.We previously showed that supplementation of the iron-exporter,ceruloplasmin,selectively corrected nigral iron elevation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)model.Ceruloplasmin delivers iron to transferrin(Tf),the extracellular iron-transporting protein.We show that Tf protein levels are decreased in the nigra of post-mortem PD brains compared with controls(−35%;n=10 each).Because Tf traffics iron away from iron-replete tissues,we hypothesized that Tf supplementation could selectively facilitate iron export from the nigra in PD.In cultured neurons,Tf treatment corrected iron accumulation,and subcutaneous Tf to mice ameliorated iron accumulation and motor deficits in the MPTP model of PD.Although these data support a role for Tf in the disease mechanism for PD,and its potential use for correcting disorders of iron overload,Tf therapy also caused systemic iron depletion,which could limit its application for PD.
