.....Here we characterize the relationship between iron homeostasis proteins and regional concentration, distribution and form of iron in MSA and PD. Methods: In post mortem brain tissue ferritin, ferroportin and transferrin were quantified by western blot and localized by immunohistochemistry. Ferritin cores were measured by Superconducting quantum interference device (Squid) measurement of isothermal remanent magnetisation (IRM). Total iron was measured by graphite furnace analysis. Results: In PD substantia nigra, tissue iron and expression of the iron export protein ferroportin increased, while the iron storage protein ferritin expression was unchanged. In the basis pontis of MSA cases, increased total iron concentration coupled with a disproportionate increase in ferritin in dysmorphic microglia and a reduction in ferroportin expression. This is supported by isothermal remanent magnetisation evidence consistent with elevated concentrations of ferritin-bound iron in MSA basis pontis. Conclusions: Conventional opinion holds that excess iron is involved in neurodegeneration. While region-specific changes in iron are evident in both PD and MSA, the mechanisms of iron dysregulation appear distinct, with a failure to export iron from the MSA basis pontis coupling with significant intracellular accumulation of ferritin-bound iron. Our preliminary data, coupled with the widespread pathology and involvement of multiple cell types, may evidence a deficit in bioavailabile iron.