Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics

被引:465
作者
Belaidi, Abdel A. [1 ]
Bush, Ashley I. [1 ]
机构
[1] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, 30 Royal Parade, Parkville, Vic 3052, Australia
基金
英国医学研究理事会; 澳大利亚研究理事会;
关键词
Alzheimers disease; chelation therapy; iron; metals; neurodegeneration; Parkinsons disease; AMYLOID PRECURSOR PROTEIN; TRANSFERRIN-BOUND IRON; TRANSGENIC MOUSE MODEL; SUBSTANTIA-NIGRA; BRAIN IRON; OXIDATIVE STRESS; CEREBROSPINAL-FLUID; ALPHA-SYNUCLEIN; FERROXIDASE ACTIVITY; REGULATORY PROTEIN-1;
D O I
10.1111/jnc.13425
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Brain iron homeostasis is increasingly recognized as a potential target for the development of drug therapies for aging-related disorders. Dysregulation of iron metabolism associated with cellular damage and oxidative stress is reported as a common event in several neurodegenerative disorders such as Alzheimers, Parkinsons, and Huntingtons diseases. Indeed, many proteins initially characterized in those diseases such as amyloid- protein, -synuclein, and huntingtin have been linked to iron neurochemistry. Iron plays a crucial role in maintaining normal physiological functions in the brain through its participation in many cellular functions such as mitochondrial respiration, myelin synthesis, and neurotransmitter synthesis and metabolism. However, excess iron is a potent source of oxidative damage through radical formation and because of the lack of a body-wide export system, a tight regulation of its uptake, transport and storage is crucial in fulfilling cellular functions while keeping its level below the toxicity threshold. In this review, we discuss the current knowledge on iron homeostasis in the brain and explore how alterations in brain iron metabolism affect neuronal function with emphasis on iron dysregulation in Alzheimers and Parkinsons diseases. Finally, we discuss recent findings implicating iron as a diagnostic and therapeutic target for Alzheimer's and Parkinson's diseases. Iron plays a fundamental role in maintaining the high metabolic and energetic requirements of the brain. However, iron has to be maintained in a delicate balance as both iron overload and iron deficiency are detrimental to the brain and can trigger neurodegeneration. Here, we discuss the current knowledge on brain iron homeostasis and its involvement in major aging-related neurodegenerative diseases. This article is part of a .
引用
收藏
页码:179 / 197
页数:19
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