Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome

James R. Connor, X. S. Wang, S. M. Patton, S. L. Menzies, J. C. Troncoso, C. J. Earley, R. P. Allen

Research output: Contribution to journalArticlepeer-review

194 Scopus citations


Background. Restless legs syndrome (RLS) is a sensory-movement disorder affecting 5 to 10% of the population. Its etiology is unknown, but MRI analyses and immunohistochemical studies on autopsy tissue suggest the substantia nigra (SN) of patients with RLS has subnormal amounts of iron. Methods: Neuromelanin cells from the SN of four RLS and four control brains were isolated by laser capture microdissection, and a profile of iron-management protein expression was obtained by immunoblot analysis. Binding assays for iron regulatory protein activity were performed on cell homogenates. Results: Ferritin, divalent metal transporter 1, ferroportin, and transferrin receptor (TfR) were decreased in RLS neuromelanin cells compared with control. Transferrin was increased in RLS neuromelanin cells. This protein profile in RLS neuromelanin cells is consistent with iron deficiency with the exception that TfR expression was decreased rather than increased. The concentration and activity of the iron regulatory proteins (IRP1 and IRP2) were analyzed to determine whether there was a functional deficit in the post-transcriptional regulatory mechanism for TfR expression. Total IRP activity, IRP1 activity, and IRP1 protein levels were decreased in RLS, but total IRP2 protein levels were not decreased in RLS. Conclusion: Restless legs syndrome may result from a defect in iron regulatory protein 1 in neuromelanin cells that promotes destabilization of the transferrin receptor mRNA, leading to cellular iron deficiency.

Original languageEnglish (US)
Pages (from-to)1563-1567
Number of pages5
Issue number9
StatePublished - May 11 2004

All Science Journal Classification (ASJC) codes

  • Clinical Neurology


Dive into the research topics of 'Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome'. Together they form a unique fingerprint.

Cite this