Iron, neuromelanin and ferritin content in the substantia nigra of normal subjects at different ages: consequences for iron storage and neurodegenerative processes

  title={Iron, neuromelanin and ferritin content in the substantia nigra of normal subjects at different ages: consequences for iron storage and neurodegenerative processes},
  author={Luigi Zecca and Mario Gallorini and Volker Sch{\"u}nemann and Alfred Xaver Trautwein and Manfred Gerlach and Peter Franz Riederer and Paolo Vezzoni and Davide Tampellini},
  journal={Journal of Neurochemistry},
Information on the molecular distribution and ageing trend of brain iron in post‐mortem material from normal subjects is scarce. Because it is known that neuromelanin and ferritin form stable complexes with iron(III), in this study we measured the concentration of iron, ferritin and neuromelanin in substantia nigra from normal subjects, aged between 1 and 90 years, dissected post mortem. Iron levels in substantia nigra were 20 ng/mg in the first year of life, had increased to 200 ng/mg by the… 

Neuromelanin and iron in human locus coeruleus and substantia nigra during aging: consequences for neuronal vulnerability

A comparative analysis of iron molecules during aging was performed in locus coeruleus (LC) and substantia nigra (SN), known targets of Parkinson’s Disease (PD) and related disorders, suggesting that in LC neurons iron mobilization and toxicity is lower than that in SN and is efficiently buffered by NM.

The role of iron and copper molecules in the neuronal vulnerability of locus coeruleus and substantia nigra during aging.

Data suggest that in LC neurons, the iron mobilization and toxicity is lower than that in SN and is efficiently buffered by NM, which may explain at least one of the reasons underlying lower vulnerability of LC compared to SN in Parkinsonian syndromes.

Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra: attenuation by dietary restriction

Iron chelation therapies and anti-inflammatory treatments may be putative ‘antibrain aging’ therapies and combining these strategies may be synergistic, it is suggested.

Changes in cytoplasmic and extracellular neuromelanin in human substantia nigra with normal aging

The absence of pronounced microgliosis, as well as a pronounced loss of NM-containing neurons, indicate the absence of neuroinflammation in human SN pars compacta during normal aging.

Lack of up‐regulation of ferritin is associated with sustained iron regulatory protein‐1 binding activity in the substantia nigra of patients with Parkinson's disease

The data of this study suggest a ‘compartmentalized’ iron accumulation in Parkinson's disease and suggest a lack of up‐regulation of ferritin expression in cytoplasmic extracts of SNpc that would be normally expected with cytosolic iron accumulation.

In vivo detection of iron and neuromelanin by transcranial sonography: A new approach for early detection of substantia nigra damage

  • L. ZeccaD. Berg G. Becker
  • Biology, Medicine
    Movement disorders : official journal of the Movement Disorder Society
  • 2005
The finding of a positive correlation between iron and ferritin levels and a negative correlation of neuromelanin content with the area of echogenicity at the SN could provide an interesting basis for diagnosis and therapeutic follow-up studies in PD.



Decreased Ferritin Levels in Brain in Parkinson's Disease

The failure of substantia nigra ferritin formation to be stimulated by increased iron levels suggests some defect in iron handling in this critical brain region in Parkinson's disease.

A Quantitative Analysis of Isoferritins in Select Regions of Aged, Parkinsonian, and Alzheimer's Diseased Brains

The analysis of isoferritin expression in brain provides insight into regional iron regulation under normal conditions and suggests a loss of ability to maintain iron homeostasis in the two disease states.

Cellular distribution of transferrin, ferritin, and iron in normal and aged human brains

The results indicate that normally oligodendrocytes contain much of the iron and iron‐binding proteins found in the brain; and an increase in age is associated with altered cellular distribution of iron‐ binding proteins, but the altered distribution is specific to glial cells.

Iron in parkinsonian and control substantia nigra—A mössbauer spectroscopy study

Mössbauer spectroscopy found no difference in the total amount of iron in SN between PD and control brains, andMeasurements performed on fresh‐frozen, formalin‐fixed, and lyophilized samples demonstrated the presence of ferric (Fe3+) iron only, both inPD and control SN.

Transition Metals, Ferritin, Glutathione, and Ascorbic Acid in Parkinsonian Brains

Reduced glutathione and the shift of the iron (II)/iron (III) ratio in favor of iron ( III) suggest that these changes might contribute to pathophysiological processes underlying PD.

Brain iron and ferritin in Parkinson's and Alzheimer's diseases

The results indicate a significant selective increase of Fe3+ and ferritin in substantia nigra zona compacta but not in zona reticulata of Parkinsonian brains, confirming the biochemical estimation of iron.

Altered systemic iron metabolism in Parkinson's disease

The results suggest the existence of a defect in the systems that regulate the synthesis of the major proteins of iron metabolism in the liver as well as the brain in Parkinson's disease that may, over time, expedite entry of iron into the brain and decrease iron in the extracellular compartment.

Isoforms of ferritin have a specific cellular distribution in the brain

The cellular distribution of the two isoforms of ferritin in the brain of adult subhuman primates is reported and considerable differences in iron sequestration and use between neurons and glia and among neuronal and glial subtypes are indicated.

Total and paramagnetic metals in human substantia nigra and its neuromelanin

  • L. ZeccaH. Swartz
  • Biology, Chemistry
    Journal of neural transmission. Parkinson's disease and dementia section
  • 1993
Compared to other regions of the mid-brain, the substantia nigra contains increased amounts of many different metal ions, and many of these metal ions are in paramagnetic valence states, which are consistent with the hypotheses that postulate a role of metal ions in promoting oxidative reactions in pigmented neurons.