Review Article

Chelators in the Treatment of Iron Accumulation in Parkinson's Disease

Figure 1

Iron-mediated cell death in PD. Reduced storage capacity in PD due to decreased ferritin expression and degeneration of nigral melatonin-containing neurons causes an increase in the reactive Fe2+ iron pool. Age-related increases in iron and a leaky BBB cause further iron accumulation. The transfer of the free iron to ferric iron, Fe3+, in the hydrogen peroxide-mediated Fenton reaction produces the highly toxic hydroxyl radical. A compromised level of glutathione exacerbates the levels of free radicals, whilst the deamination and autoxidation of dopamine produces further H2O2. The subsequent oxidative stress can then elicit a range of cytotoxic reactions including protein misfolding, lipid peroxidation (which, in turn, can cause α-synuclein aggregation), mitochondrial dysfunction, and activation of glial cells. These various insults can induce cell death by apoptosis, causing further degeneration.
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