@article{IsaiasTrujilloSummersetal.2016,
  author    = {Isaias, Ioannis U. and Trujillo, Paula and Summers, Paul and Marotta, Giorgio and Mainardi, Luca and Pezzoli, Gianni and Zecca, Luigi and Costa, Antonella},
  title     = {Neuromelanin Imaging and Dopaminergic Loss in Parkinson's Disease},
  series = {Frontiers in Aging Neuroscience},
  volume    = {8},
  journal   = {Frontiers in Aging Neuroscience},
  number    = {196},
  doi       = {10.3389/fnagi.2016.00196},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164046},
  year      = {2016},
  abstract  = {Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the major pathologic substrate is a loss of dopaminergic neurons from the substantia nigra. Our main objective was to determine the correspondence between changes in the substantia nigra, evident in neuromelanin and iron sensitive magnetic resonance imaging (MRI), and dopaminergic striatal innervation loss in patients with PD. Eighteen patients and 18 healthy control subjects were included in the study. Using neuromelanin-MRI, we measured the volume of the substantia nigra and the contrast-to-noise-ratio between substantia nigra and a background region. The apparent transverse relaxation rate and magnetic susceptibility of the substantia nigra were calculated from dual-echo MRI. Striatal dopaminergic innervation was measured as density of dopamine transporter (DAT) by means of single-photon emission computed tomography and [123I] N-ω-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane. Patients showed a reduced volume of the substantia nigra and contrast-to-noise-ratio and both positively correlated with the corresponding striatal DAT density. The apparent transverse relaxation rate and magnetic susceptibility values of the substantia nigra did not differ between patients and healthy controls. The best predictor of DAT reduction was the volume of the substantia nigra. Clinical and imaging correlations were also investigated for the locus coeruleus. Our results suggest that neuromelanin-MRI can be used for quantifying substantia nigra pathology in PD where it closely correlates with dopaminergic striatal innervation loss. Longitudinal studies should further explore the role of Neuromelanin-MRI as an imaging biomarker of PD, especially for subjects at risk of developing the disease.},
  language  = {en}
}
@article{PlumSteinbachAttemsetal.2016,
  author    = {Plum, Sarah and Steinbach, Simone and Attems, Johannes and Keers, Sharon and Riederer, Peter and Gerlach, Manfred and May, Caroline and Marcus, Katrin},
  title     = {Proteomic characterization of neuromelanin granules isolated from human substantia nigra by laser-microdissection},
  series = {Scientific Reports},
  volume    = {6},
  journal   = {Scientific Reports},
  number    = {37139},
  doi       = {10.1038/srep37139},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167507},
  year      = {2016},
  abstract  = {Neuromelanin is a complex polymer pigment found primarily in the dopaminergic neurons of human substantia nigra. Neuromelanin pigment is stored in granules including a protein matrix and lipid droplets. Neuromelanin granules are yet only partially characterised regarding their structure and function. To clarify the exact function of neuromelanin granules in humans, their enrichment and in-depth characterization from human substantia nigra is necessary. Previously published global proteome studies of neuromelanin granules in human substantia nigra required high tissue amounts. Due to the limited availability of human brain tissue we established a new method based on laser microdissection combined with mass spectrometry for the isolation and analysis of neuromelanin granules. With this method it is possible for the first time to isolate a sufficient amount of neuromelanin granules for global proteomics analysis from ten 10 μm tissue sections. In total 1,000 proteins were identified associated with neuromelanin granules. More than 68\% of those proteins were also identified in previously performed studies. Our results confirm and further extend previously described findings, supporting the connection of neuromelanin granules to iron homeostasis and lysosomes or endosomes. Hence, this method is suitable for the donor specific enrichment and proteomic analysis of neuromelanin granules.},
  language  = {en}
}