The Department of Molecular, Cellular, and Developmental Biology, the University of Michigan, 3089 Natural Science Building (Kraus), 830 North University, Ann Arbor, MI 48109, USA.
Future Med Chem. 2010 Jan;2(1):51-64. doi: 10.4155/fmc.09.140.
Trace metals such as iron, copper, zinc, manganese, and cobalt are essential cofactors for many cellular enzymes. Extensive research on iron, the most abundant transition metal in biology, has contributed to an increased understanding of the molecular machinery involved in maintaining its homeostasis in mammalian peripheral tissues. However, the cellular and intercellular iron transport mechanisms in the central nervous system (CNS) are still poorly understood. Accumulating evidence suggests that impaired iron metabolism is an initial cause of neurodegeneration, and several common genetic and sporadic neurodegenerative disorders have been proposed to be associated with dysregulated CNS iron homeostasis. This review aims to provide a summary of the molecular mechanisms of brain iron transport. Our discussion is focused on iron transport across endothelial cells of the blood-brain barrier and within the neuro- and glial-vascular units of the brain, with the aim of revealing novel therapeutic targets for neurodegenerative and CNS disorders.
痕量金属如铁、铜、锌、锰和钴是许多细胞酶的必需辅助因子。对生物学中最丰富的过渡金属铁的广泛研究，有助于增加对维持哺乳动物外周组织铁平衡的分子机制的理解。然而，中枢神经系统 (CNS) 中的细胞内和细胞间铁转运机制仍知之甚少。越来越多的证据表明，铁代谢失调是神经退行性变的最初原因，并且已经提出几种常见的遗传和散发性神经退行性疾病与中枢神经系统铁稳态失调有关。本综述旨在提供脑铁转运的分子机制概述。我们的讨论集中在血脑屏障内皮细胞和脑的神经胶质血管单元内的铁转运，目的是为神经退行性疾病和中枢神经系统疾病揭示新的治疗靶点。
