TY - JOUR
T1 - A quantitative analysis of isoferritins in select regions of aged, Parkinsonian, and Alzheimer's diseased brains
AU - Connor, James R.
AU - Snyder, Brian S.
AU - Arosio, Paolo
AU - Loeffler, David A.
AU - LeWitt, Peter
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1995/8
Y1 - 1995/8
N2 - The brain requires a ready supply of iron for normal neurological function, but free iron is toxic. Consequently, iron bioavailability must be stringently regulated. Recent evidence has suggested that the brain iron regulatory system is dysfunctional in neurological disorders such as Alzheimer's and Parkinson's diseases (AD and PD, respectively). A key component of the iron regulatory system in the brain is ferritin. Ferritin consists of 24 subunits, which are distinguished as either a heavy-chain (H) or light-chain (L) isoform. These peptide subunits are genetically and functionally distinct. Thus, the ability to investigate separately the types of ferritin in brain should provide insight into iron management at both the cellular and the molecular level. In this study, the ratio of isoferritins was determined in select regions of adult elderly AD and PD human brains. The H-rich ferritin was more abundant in the young brain, except in the globus pallidus where the ratio of H/L ferritin was 1:1. The balance of H/L isoferritins was influenced by age, brain region, and disease state. With normal aging, both H and L ferritin increased; however, the age-associated increase in isoferritins generally failed to occur in AD and PD brain tissue. The imbalance in H/L isoferritins was disease and region specific. For example, in frontal cortex, there was a dramatic (fivefold) increase in the ratio of H/L ferritin in AD brains but not in PD brains. In PD, caudate and putamen H/L ratios were higher than in AD and the elderly control group. 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. This latter observation provides further evidence of dysfunction of iron homeostatic mechanisms in AD and PD and may contribute significantly to understanding the underlying pathogenesis of each, particularly in relation to iron-induced oxidative damage.
AB - The brain requires a ready supply of iron for normal neurological function, but free iron is toxic. Consequently, iron bioavailability must be stringently regulated. Recent evidence has suggested that the brain iron regulatory system is dysfunctional in neurological disorders such as Alzheimer's and Parkinson's diseases (AD and PD, respectively). A key component of the iron regulatory system in the brain is ferritin. Ferritin consists of 24 subunits, which are distinguished as either a heavy-chain (H) or light-chain (L) isoform. These peptide subunits are genetically and functionally distinct. Thus, the ability to investigate separately the types of ferritin in brain should provide insight into iron management at both the cellular and the molecular level. In this study, the ratio of isoferritins was determined in select regions of adult elderly AD and PD human brains. The H-rich ferritin was more abundant in the young brain, except in the globus pallidus where the ratio of H/L ferritin was 1:1. The balance of H/L isoferritins was influenced by age, brain region, and disease state. With normal aging, both H and L ferritin increased; however, the age-associated increase in isoferritins generally failed to occur in AD and PD brain tissue. The imbalance in H/L isoferritins was disease and region specific. For example, in frontal cortex, there was a dramatic (fivefold) increase in the ratio of H/L ferritin in AD brains but not in PD brains. In PD, caudate and putamen H/L ratios were higher than in AD and the elderly control group. 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. This latter observation provides further evidence of dysfunction of iron homeostatic mechanisms in AD and PD and may contribute significantly to understanding the underlying pathogenesis of each, particularly in relation to iron-induced oxidative damage.
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M3 - Article
C2 - 7616228
AN - SCOPUS:0029092802
SN - 0022-3042
VL - 65
SP - 717
EP - 724
JO - Journal of neurochemistry
JF - Journal of neurochemistry
IS - 2
ER -