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

Abstract

Abstract 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 Alzheimer′s, Parkinson′s, and Huntington′s diseases. Indeed, many proteins initially characterized in those diseases such as amyloid‐β protein, α‐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 Alzheimer′s and Parkinson′s diseases. Finally, we discuss recent findings implicating iron as a diagnostic and therapeutic target for Alzheimer's and Parkinson's diseases. image 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 special issue on Parkinson disease .

Keywords

Affiliated Institutions

• Florey Institute of Neuroscience and Mental Health AU
• The University of Melbourne AU

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