DOI 10.1007/s00702-005-0448-4 J Neural Transm (2006) 113: 769–774 Is neuromelanin changed in Parkinson’s disease? Investigations by magnetic spectroscopies M. Fasano 1 , B. Bergamasco 2;3 , and L. Lopiano 2 1 Department of Structural and Functional Biology, and Centre of Neuroscience, University of Insubria, Busto Arsizio (VA), 2 Department of Neuroscience, University of Torino, Torino, and 3 Salvatore Maugeri Foundation, I.R.C.C.S., Pavia, Italy Received September 1, 2005; accepted December 20, 2005 Published online May 12, 2006; # Springer-Verlag 2006 Summary. Human mesencephalic neuromel- anin (NM) is characterized by an irregular, undefined structure, making its characteriza- tion by usual physico-chemical methodolo- gies quite difficult. NM isolated from controls and from Parkinson’s Disease (PD) patients was compared by high-resolution solid-state nuclear magnetic resonance (NMR). The pig- ment from PD patients appeared to be mainly composed of highly cross-linked, protease- resistant lipo-proteic material, with disappear- ance of melanin NMR resonances, suggesting melanin breakout due to oxidative stress con- ditions. Moreover, alpha-synuclein was de- tected in NM of PD patients and controls after cleavage of the melanin backbone under solubilizing conditions. NM stores iron ions as oxyhydroxide iron clusters containing thousands of iron atoms. Electron Paramagnetic Resonance (EPR) investigations and magnetic suscep- tibility measurements confirmed the occur- rence of magnetic coupling among iron atoms, whereas in synthetic melanin the oc- currence of isolated Fe 3þ ions was evident. NM from PD patients showed a lower total magnetization, possibly suggesting a progres- sive Fe migration from its storage environ- ment (i.e., NM) to the cytosol. Keywords: Iron, magnetic resonance, neuro- melanin. Introduction Neuromelanin (NM) is a pigment belonging to the melanin family, responsible for the dark color of the midbrain region called sub- stantia nigra pars compacta (SNpc). This area of the human brain undergoes severe degen- eration during the progression of Parkinson’s Disease (PD). Histological evidence shows that the more pigmented neurons are the first ones to degenerate, suggesting thus that NM depletion does not occur at random; conversely, it has been reported that the less pigmented ventral tier of SN is the first to degenerate in PD, with a more extended cell loss with respect to heavily pigmented regions. Neuropathologically, PD is char- acterized by eosinophilic cytoplasmic inclu- sions, so called filamentous Lewy bodies, in dopaminergic neurons of SNpc and of other pigmented nuclei. Lewy bodies are mainly composed by alpha-synuclein, a small (14 kDa)