REGIONAL DISTRIBUTION OF IRON AND IRON-REGULATORY PROTEINS IN THE BRAIN IN AGING AND ALZHEIMERS-DISEASE
REGIONAL DISTRIBUTION OF IRON AND IRON-REGULATORY PROTEINS IN THE BRAIN IN AGING AND ALZHEIMERS-DISEASE
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DOI：
10.1002/jnr.490310214
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发表时间：
1992-02-01
影响因子：
4.2
通讯作者：
MUFSON, EJ
中科院分区：
文献类型：
--
作者：
CONNOR, JR;SNYDER, BS;MUFSON, EJ
铁元素对正常的神经功能非常重要，它在所有器官系统中都受到高度调节。然而，直到最近，铁在神经系统中的调节还很少受到关注。本研究从尸体解剖收集的材料中定量比较了人脑皮层三个区域中主要的铁调节蛋白、转铁蛋白和铁蛋白以及铁本身的水平。研究对象分为三组：1)正常成人（65岁以下），2)老年（65岁以下）和3)阿尔茨海默病。正常情况下，转铁蛋白在白质中比在灰质中更丰富。铁蛋白的含量是转铁蛋白的10倍左右，并且和铁一样均匀分布在灰质和白质中。在阿尔茨海默病中，转铁蛋白持续下降，特别是在大脑皮层各区域的白质中，而铁和铁蛋白的变化则不一致。本研究的观察结果与我们的一般假设一致，即衰老的大脑中的铁稳态被破坏，铁调节蛋白的改变在阿尔茨海默病中加剧。转铁蛋白水平的下降可能表明大脑中铁的活动性和随后的利用率下降。这种铁可用性的降低可能在阿尔茨海默病中发生的神经元变性和增加的过氧化损伤中发挥重要作用。
It is well established that iron, which is considerable importance for normal neurological function, is highly regulated in all organ systems. However, until recently, iron regulation in the nervous system has received little attention. This study quantitatively compares the levels of the major iron-regulatory proteins, transferrin and ferritin, and iron itself in three cerebral cortical regions of the human brain from material collected at autopsy. Three groups were studied: 1) normal adult (under 65 yr of age), 2) aged (> 65), and 3) Alzheimer's disease. Normally, transferrin is more abundant in white matter than in gray matter. Ferritin is approximately 10 x more abundant than transferrin throughout the brain regions examined and is evenly distributed, as is iron, in the gray and white matter. In Alzheimer's disease transferrin is consistently decreased particularly in the white matter of the various cerebral cortical regions examined whereas the iron and ferritin changes are inconsistent. The observations in this study are consistent with our general hypothesis that iron homeostasis is disrupted in the aging brain and the alterations in iron-regulatory proteins are exacerbated in Alzheimer's disease. The decrease in transferrin levels could indicate a decreased mobility and subsequent utilization of iron in the brain. Such a decrease in iron availability could play a significant role in neuronal degeneration and increased peroxidative damage known to occur in Alzheimer's disease.