Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To gain insight into the role of microglia in the formation of senile plaques (SP), especially in the generation of the two major molecular species of amyloid beta protein (A beta) with different carboxyl (C)-termini, A beta 40 and A beta 42(43), we conducted double immunolabelling studies on tissue sections from the brains of Alzheimer's disease (AD) and non-demented aged individuals using antibodies to the C-termini of A beta and ferritin, a marker for microglia. All SP were A beta 42(43)-positive in AD as well as in non-demented individuals, only a proportion of which were A beta 40-positive. Both in AD and in non-demented individuals, approximately 2/3 of the A beta 40-positive SP were typical SP with amyloid cores, these being almost invariably associated with microglia. A beta 40-positive, uncored SP were also frequently associated with microglia (mean, 74%), whereas only 24% of A beta 40-negative, uncored SP contained microglia. These results suggest that microglia may play a role in the maturation of SP, especially in the generation of A beta 40.
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PMID:Association of A beta 40-positive senile plaques with microglial cells in the brains of patients with Alzheimer's disease and in non-demented aged individuals. 873 77

The extent of microglial cell activation (microglial cell load) was estimated by image analysis of ferritin-immunostained sections of frontal cortex from 72 patients with pathologically confirmed Alzheimer's disease (AD), and correlated with the amount of pathological tau and amyloid beta protein (Abeta), as both Abeta(40) and Abeta(42) load, in adjacent sections of the same cases. Microglial cell load did not correlate with either Abeta(40) or Abeta(42) load but was significantly correlated with pathological tau load. Microglial cell load was unrelated to age at onset of disease or duration of illness. It is possible that because the presence of microglial cells predates that of pathological tau proteins within the cerebral cortex in AD, neurofibrillary damage to nerve cells may stem from the release of proinflammatory and other potentially neurotoxic molecules from microglial cells.
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PMID:Pathological relationships between microglial cell activity and tau and amyloid beta protein in patients with Alzheimer's disease. 1238 24

The essential metals iron, zinc and copper deposit near the Abeta (amyloid beta-peptide) plaques in the brain cortex of AD (Alzheimer's disease) patients. Plaque-associated iron and zinc are in neurotoxic excess at 1 mM concentrations. APP (amyloid precursor protein) is a single transmembrane metalloprotein cleaved to generate the 40-42-amino-acid Abetas, which exhibit metal-catalysed neurotoxicity. In health, ubiquitous APP is cleaved in a non-amyloidogenic pathway within its Abeta domain to release the neuroprotective APP ectodomain, APP(s). To adapt and counteract metal-catalysed oxidative stress, as during reperfusion from stroke, iron and cytokines induce the translation of both APP and ferritin (an iron storage protein) by similar mechanisms. We reported that APP was regulated at the translational level by active IL (interleukin)-1 (IL-1-responsive acute box) and IRE (iron-responsive element) RNA stem-loops in the 5' untranslated region of APP mRNA. The APP IRE is homologous with the canonical IRE RNA stem-loop that binds the iron regulatory proteins (IRP1 and IRP2) to control intracellular iron homoeostasis by modulating ferritin mRNA translation and transferrin receptor mRNA stability. The APP IRE interacts with IRP1 (cytoplasmic cis-aconitase), whereas the canonical H-ferritin IRE RNA stem-loop binds to IRP2 in neural cell lines, and in human brain cortex tissue and in human blood lysates. The same constellation of RNA-binding proteins [IRP1/IRP2/poly(C) binding protein] control ferritin and APP translation with implications for the biology of metals in AD.
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PMID:Iron and the translation of the amyloid precursor protein (APP) and ferritin mRNAs: riboregulation against neural oxidative damage in Alzheimer's disease. 1902 41