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Abnormal localization of iron regulatory protein in Alzheimer's disease.

Abstract
A role for altered iron metabolism in the pathogenesis of Alzheimer's disease has been suggested by several reports associating the cardinal neuropathologic lesions with markers of free radical-induced damage and redox-active iron. We hypothesized that the abnormal distribution of iron in Alzheimer brain might result from alterations in iron regulatory proteins (IRP) such as IRP-1 and IRP-2, the main control elements of cellular iron homeostasis. Here, we report that while IRP-1 is present at similar levels in both Alzheimer and control brain tissue, IRP-2 shows striking differences and is associated with intraneuronal lesions, including neurofibrillary tangles, senile plaque neurites and neuropil threads. Since IRP-2 colocalizes with redox-active iron, our results suggest that alterations in IRP-2 might be directly linked to impaired iron homeostasis in Alzheimer's disease.
AuthorsM A Smith, K Wehr, P L Harris, S L Siedlak, J R Connor, G Perry
JournalBrain research (Brain Res) Vol. 788 Issue 1-2 Pg. 232-6 (Mar 30 1998) ISSN: 0006-8993 [Print] NETHERLANDS
PMID9555030 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
CopyrightCopyright 1998 Elsevier Science B.V.
Chemical References
  • Iron-Regulatory Proteins
  • Iron-Sulfur Proteins
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Iron Regulatory Protein 1
  • Iron Regulatory Protein 2
Topics
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease (metabolism)
  • Case-Control Studies
  • Energy Metabolism (physiology)
  • Homeostasis
  • Humans
  • Immunohistochemistry
  • Iron Regulatory Protein 1
  • Iron Regulatory Protein 2
  • Iron-Regulatory Proteins
  • Iron-Sulfur Proteins (analysis)
  • Middle Aged
  • Nerve Tissue Proteins (analysis)
  • Oxidation-Reduction
  • Oxidative Stress (physiology)
  • RNA-Binding Proteins (analysis)

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