Neuromelanin, Iron and Ferritin in Locus Ceruleus as Potential Determinants of Selective Neuronal Vulnerability

Luigi Zecca, M.D., Ph.D.

Institute of Advanced Biomedical Technologies-CNR, Segrate, Italy

Abstract

Another area of the basal ganglia, the locus ceruleus (LC), is nearly as damaged in PD brains as is the substantia nigra (SN). The healthy LC also contains high levels of neuromelanin, a substance thought to have the ability to protect against against neurotoxicity. Dr. Luigi Zecca and his colleagues at the Institute of Advance Biomedical Technologies (Segrate, Itay) will confirm the relationship between the cell losses of the LC and the presence of depression and dementia in PD patients, seeking to determine both the concentrations to trace metals (iron and ferritin) in PD brain tissue and methods of decreasing their effects on the degenerative process. Their work will be done in tissue autopsied from healthy humans who died without neurologic or psychiatric disease and compared with tissue from known PD patients.

Progress Report (as of 8/2002)

Dr. Luigi Zecca (Institute of Advanced Biomedical Technologies in Segrate, Italy) reports that his theory of the cause of lesser damage to the locus ceruleus (LC) than to the substantia nigra (SN) in PD has been proven. Comparing autopsied tissue from healthy people with that from known PD patients, he and his colleagues found less iron in the LCs than in SNs of the patients. What iron toxicity is present in the LC is thus less conducive to oxidative stress, and is better blocked than in the SN because of higher H-ferritin/iron and higher neuromelanin/iron ratios. Neuromelanin (NM) seems to be able to provide protection based on its ability to chelate trace metals and accumulate toxins, “flushing” them from the brain.