Role of iron in pathogenesis of Parkinson disease

Abstract

Parkinson’s disease is one of the most frequent human neurodegenerations. Motor symptoms of Parkinson’s disease are the consequence of the destruction of nervous cells in the substantia nigra (SN), a small (about 500 mg) structure located deep in human brain. The concentration of iron in SN is comparable to that in liver and is equal to about 180 ± 60 ng/mg of wet tissue and the iron in SN is mostly bound to ferritin. For many years it has been believed that the degeneration of nervous cells in SN in Parkinson’s disease is related to an important increase in the concentration of iron. Our own studies based on Mossbauer spectroscopy and other studies conducted with the use of various techniques have not confirmed this finding. The ratio of the concentration of iron in PD vs. control SN evaluated by Mossbauer spectroscopy was found to be equal 1.00 ± 0.13. We also confirmed that most of iron in SN is located within ferritin. ELISA studies demonstrated a significant decrease in L ferritin in parkinsonian SN compared to the control group. As L-ferritin is related to safe keeping of iron within the ferritin shell, its decrease may lead to an efflux of iron and increase in the concentration of labile iron. Indeed our studies did show a difference in the concentration of labile iron between PD and control SN (135 ± 10 ng/g vs. 76 ± 5 ng/g). This labile iron, which may initiate Fenton reaction, may be the cause of the oxidative stress leading to the death of nervous cells in PD.