Abstract
Iron dyshomeostasis can cause neuronal damage to iron-sensitive brain regions. Neurodegeneration with brain iron accumulation reflects a group of disorders caused by iron overload in the basal ganglia. High iron levels and iron related pathogenic triggers have also been implicated in sporadic neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple system atrophy (MSA). Iron-induced dyshomeostasis within vulnerable brain regions is still insufficiently understood. Here, we summarize the modes of action by which iron might act as primary or secondary disease trigger in neurodegenerative disorders. In addition, available treatment options targeting brain iron dysregulation and the use of iron as biomarker in prodromal stages are critically discussed to address the question of cause or consequence.
Highlights
Iron is involved in an abundant number of cellular processes in the brain including mitochondrial respiration, myelin synthesis, DNA synthesis, oxygen transportation, neurotransmitter synthesis and cellular metabolism (Stankiewicz and Brass, 2009; Ward et al, 2014)
Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies, amyotrophic lateral sclerosis, Huntington’s disease (HD), frontotemporal dementia, corticobasal degeneration, and progressive supranuclear palsy (PSP) are primarily characterized by the deposition of insoluble protein aggregates which colocalize with iron (Coffey et al, 1989; Berg and Hochstrasser, 2006; Muller and Leavitt, 2014; Wang et al, 2016; Fernández et al, 2017; Lee et al, 2017; Sheelakumari et al, 2017; Kaindlstorfer et al, 2018; Lane et al, 2018; Moreau et al, 2018), suggesting a link between those clinically and pathologically distinct disease entities
This raises the question whether iron dyshomeostasis represents a critical factor in initiating neurodegeneration, whether it contributes to acceleration of widespread pathology as a result of nerve cell death and the consecutive release of intracellular components or whether neurodegeneration and iron accumulation constitute two completely unrelated events appearing in parallel
Summary
Iron is involved in an abundant number of cellular processes in the brain including mitochondrial respiration, myelin synthesis, DNA synthesis, oxygen transportation, neurotransmitter synthesis and cellular metabolism (Stankiewicz and Brass, 2009; Ward et al, 2014). Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies, amyotrophic lateral sclerosis, Huntington’s disease (HD), frontotemporal dementia, corticobasal degeneration, and progressive supranuclear palsy (PSP) are primarily characterized by the deposition of insoluble protein aggregates which colocalize with iron (Coffey et al, 1989; Berg and Hochstrasser, 2006; Muller and Leavitt, 2014; Wang et al, 2016; Fernández et al, 2017; Lee et al, 2017; Sheelakumari et al, 2017; Kaindlstorfer et al, 2018; Lane et al, 2018; Moreau et al, 2018), suggesting a link between those clinically and pathologically distinct disease entities This raises the question whether iron dyshomeostasis represents a critical factor in initiating neurodegeneration, whether it contributes to acceleration of widespread pathology as a result of nerve cell death and the consecutive release of intracellular components or whether neurodegeneration and iron accumulation constitute two completely unrelated events appearing in parallel. In this review we aim to outline the potential links between pathophysiological mechanisms and the role of iron in neurodegeneration
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
