Background: Iron status is higher in the substantia nigra than in other brain regions but can fluctuate as function of diet and genetics and disease. Of particular note is the compartmentalization of the iron-enrichment in this region; the pars reticulata contains higher levels of stainable iron as compared to the pars compacta. The latter area is where the dopaminergic neurons reside. How this compartmentalization impacts the interpretation of data that iron contributes to cell death as in Parkinson's disease or iron deficiency contributes to altered dopaminergic activity is unknown. Nonetheless, that iron can influence neuronal cell death and dopamine function is clear.
Methods: The mechanisms by which iron may be managed in the substantia nigra, particularly in the neuromelanin cells where minimal levels of ferritin the iron storage protein have been detected are addressed. The current approaches to detect iron in the substantia nigra are also reviewed. In addition, the potential mechanisms by which iron enrichment may occur in the substantia nigra are explored.
General significance: This review attempts to provide a critical evaluation of the many avenues of exploration into the role of iron in one of the most iron-enriched and clinically investigated areas of the brain, the substantia nigra.