The role of iron in brain ageing and neurodegenerative disorders

Lancet Neurol. 2014 Oct;13(10):1045-1060. doi: 10.1016/S1474-4422(14)70117-6.

Ward RJ, Zucca FA, Duyn JH, Crichton RR, Zecca L.

SUMMARY:

In the CNS, iron in several proteins is involved in many important processes such as oxygen transportation, oxidative phosphorylation, myelin production, and the synthesis and metabolism of neurotransmitters. Abnormal iron homoeostasis can induce cellular damage through hydroxyl radical production, which can cause the oxidation and modification of lipids, proteins, carbohydrates, and DNA. During ageing, different iron complexes accumulate in brain regions associated with motor and cognitive impairment. In various neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, changes in iron homoeostasis result in altered cellular iron distribution and accumulation. MRI can often identify these changes, thus providing a potential diagnostic biomarker of neurodegenerative diseases. An important avenue to reduce iron accumulation is the use of iron chelators that are able to cross the blood-brain barrier, penetrate cells, and reduce excessive iron accumulation, thereby affording neuroprotection.