Transferrin protects against parkinsonian neurotoxicity and is deficient in parkinson’s substantia nigra

Abstract

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 i..