FERRITIN AND TRANSFERRIN IN CNS AGING &DISEASE

Project: Research project

Description

The long term goal of this research project is to understand iron
regulation in the nervous system and how perturbations in iron metabolism
may have a role in neurodegenerative disorders. However, although this
research program is currently focusing on iron, the absence of the word
"iron" in the title of this application is deliberate. Because
transferrin, the iron mobilization protein, and ferritin, the iron storage
protein, are known to bind a number of cations in addition to iron, the
ultimate goal of this research project may lie in understanding metal
regulation in the brain. The first metal in addition to iron that we have
chosen to examine is aluminum because of the potential through
controversial role of aluminum in Alzheimer's disease. The objectives of
this proposal are: (i) to demonstrate the cell types(s) which contain
transferrin, the transferrin receptor, and/or ferritin in the normal human
CNS; (ii) to determine the protein and mRNA levels of the major components
of the iron system in different brain regions; (iii) to determine
alterations in the distribution and concentration of the major iron
components (both protein and mRNA in Alzheimer's and Parkinson's diseases;
(iv) to determine if areas of high ferritin and transferrin receptor
density coincide with high levels of aluminum in Alzheimer's brain tissue;
(v) to demonstrate that aluminum complexed to transferrin will compete
efficiently with transferrin-iron for the transferrin receptor in the brain
and in vitro; (vi) to determine the ability of transferrin-aluminum
(relative to transferrin-iron) to regulate transferrin and ferritin
synthesis in culture; (vii) to determine if a sialovariant form of
transferrin exists in a higher ratio than normal in brain, CSF or plasma in
Alzheimer's or Parkinson's Disease. The potential significance of this
latter objective lies in the possibility of a biological marker for
Alzheimer's or Parkinson's Disease. The technical approaches utilized in
this proposal include immunohistochemistry, immunoassay, immunoblots,
northern blots, and receptor binding. The results of the studies in this
proposal will immediately contribute to helping understand the number of
neurological disorders thought to be associated with a disruption in iron
metabolism. The potential for transferrin and ferritin to modulate a
number of metals may lead to new areas of investigation in the
neurosciences.
StatusFinished
Effective start/end date5/1/904/30/94

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $144,708.00

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Central Nervous System Diseases
Transferrin
Ferritins
Iron
Aluminum
Parkinson Disease
Transferrin Receptors
Brain
Alzheimer Disease
Metals
Messenger RNA
Proteins
Aptitude
Immunoassay
Research
Neurodegenerative Diseases
Northern Blotting
Nervous System
Cations
Biomarkers