Targeting Mitochondrial Metal Dyshomeostasis for the Treatment of Neurodegeneration

Liddell, Jeffrey R.

doi:10.2217/nmt.15.19

Cited by 13 publications

(7 citation statements)

References 231 publications

(216 reference statements)

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“…They are the site of Fe-S cluster assembly and heme synthesis. Fe-S clusters are integral for the function of many proteins including complex I of the electron transport chain and other iron metabolism proteins (Liddell, 2015). Of these, the bifunctional cytosolic protein aconitase/iron regulatory protein 1 is central to the regulation of iron metabolism.…”

Section: The Iron-mitochondria Nexusmentioning

confidence: 99%

Nexus between mitochondrial function, iron, copper and glutathione in Parkinson's disease

Liddell

White

2018

Neurochemistry International

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Parkinson's disease is neuropathologically characterised by loss of catecholamine neurons in vulnerable brain regions including substantia nigra pars compacta and locus coeruleus. This review discusses how the susceptibility of these regions is defined by their shared biochemical characteristics that differentiate them from other neurons. Parkinson's disease is biochemically characterised by mitochondrial dysfunction, accumulation of iron, diminished copper content and depleted glutathione levels in these regions. This review also discusses this neuropathology, and provides evidence for how these pathological features are mechanistically linked to each other. This leads to the conclusion that disruption of mitochondrial function, or iron, copper or glutathione metabolism in isolation provokes the pathological impairment of them all. This creates a vicious cycle that drives pathology leading to mitochondrial failure and neuronal cell death in vulnerable brain regions.

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Section: The Iron-mitochondria Nexusmentioning

confidence: 99%

Nexus between mitochondrial function, iron, copper and glutathione in Parkinson's disease

Liddell

White

2018

Neurochemistry International

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“…In addition, mitochondria are necessary calcium-buffering organelles in neurons as they regulate local calcium dynamics to control neurotransmitter release [ 9 ]. Mitochondrial dysfunction has been implicated in a variety of diseases, and is a causative factor in several neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), autism, and amyotrophic lateral sclerosis (ALS) [ 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Metal-Induced Mitochondrial Dysfunction in Neurological Disorders

Cheng

Yang

Tao

et al. 2021

Toxics

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Metals are actively involved in multiple catalytic physiological activities. However, metal overload may result in neurotoxicity as it increases formation of reactive oxygen species (ROS) and elevates oxidative stress in the nervous system. Mitochondria are a key target of metal-induced toxicity, given their role in energy production. As the brain consumes a large amount of energy, mitochondrial dysfunction and the subsequent decrease in levels of ATP may significantly disrupt brain function, resulting in neuronal cell death and ensuing neurological disorders. Here, we address contemporary studies on metal-induced mitochondrial dysfunction and its impact on the nervous system.

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“…In several other neurodegenerative disorders including AD, PD, HD, amyotrophic lateral sclerosis, multiple sclerosis, and Friedreich's ataxia, loss of iron homeostasis, oxidative stress, and mitochondrial injury have been suggested to constitute a common pathway to cell death although the pathological hallmarks of these neurodegenerative diseases vary. Currently, a key question of why iron increases abnormally in some brain regions of these diseases has not been answered.…”

Section: Brain Iron Misregulation Is a Common Pathway In Neurodegenermentioning

confidence: 99%

Hepcidin and its therapeutic potential in neurodegenerative disorders

Qian

2019

Medicinal Research Reviews

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Abnormally high brain iron, resulting from the disrupted expression or function of proteins involved in iron metabolism in the brain, is an initial cause of neuronal death in neuroferritinopathy and aceruloplasminemia, and also plays a causative role in at least some of the other neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Friedreich's ataxia. As such, iron is believed to be a novel target for pharmacological intervention in these disorders. Reducing iron toward normal levels or hampering the increases in iron associated with age in the brain is a promising therapeutic strategy for all iron‐related neurodegenerative disorders. Hepcidin is a crucial regulator of iron homeostasis in the brain. Recent studies have suggested that upregulating brain hepcidin levels can significantly reduce brain iron content through the regulation of iron transport protein expression in the blood‐brain barrier and in neurons and astrocytes. In this review, we focus on the discussion of the therapeutic potential of hepcidin in iron‐associated neurodegenerative diseases and also provide a systematic overview of recent research progress on how misregulated brain iron metabolism is involved in the development of multiple neurodegenerative disorders.

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Targeting Mitochondrial Metal Dyshomeostasis for the Treatment of Neurodegeneration

Cited by 13 publications

References 231 publications

Nexus between mitochondrial function, iron, copper and glutathione in Parkinson's disease

Nexus between mitochondrial function, iron, copper and glutathione in Parkinson's disease

Mechanisms of Metal-Induced Mitochondrial Dysfunction in Neurological Disorders

Hepcidin and its therapeutic potential in neurodegenerative disorders

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