Iron overload induced by IRP2 gene knockout aggravates symptoms of Parkinson's disease

Ci, Yunzhe; Li, Haiyan; You, Linhao; Jin, Yu; Zhou, Rui; Gao, Guofen; Hoi, Maggie Pui Man; Wang, Chunyan; Chang, Yan‐Zhong; Yu, Peng

doi:10.1016/j.neuint.2019.104657

Cited by 15 publications

(9 citation statements)

References 38 publications

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“…In a recent work, it was shown that mice lacking the expression of IRP2 have iron deposits and increased expression of FTL. Recent data showed that this is linked with aggravated neuronal apoptosis and Parkinsonism symptoms [80]. Regarding Alzheimer's Disease (AD), recent works claim that high ferritin levels contribute to an accelerated pathology [81].…”

Section: Neurodegenerative Disordersmentioning

confidence: 99%

Ferritin: An Inflammatory Player Keeping Iron at the Core of Pathogen-Host Interactions

2020

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Iron is an essential element for virtually all cell types due to its role in energy metabolism, nucleic acid synthesis and cell proliferation. Nevertheless, if free, iron induces cellular and organ damage through the formation of free radicals. Thus, iron levels must be firmly controlled. During infection, both host and microbe need to access iron and avoid its toxicity. Alterations in serum and cellular iron have been reported as important markers of pathology. In this regard, ferritin, first discovered as an iron storage protein, has emerged as a biomarker not only in iron-related disorders but also in inflammatory diseases, or diseases in which inflammation has a central role such as cancer, neurodegeneration or infection. The basic research on ferritin identification and functions, as well as its role in diseases with an inflammatory component and its potential as a target in host-directed therapies, are the main considerations of this review.

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Section: Neurodegenerative Disordersmentioning

confidence: 99%

Ferritin: An Inflammatory Player Keeping Iron at the Core of Pathogen-Host Interactions

2020

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“…10,11 The iron accumulation in the SN via the deletion of the Iron regulatory protein 2 exacerbated dopaminergic neuron apoptosis and Parkinsonism symptoms. 12 High dietary iron increased the death of dopaminergic neuron, and reduced the content of dopamine in transgenic mice with overexpressing human A53T α-syn. 13 A large accumulation of iron can produce reactive oxygen species, increase oxidative stress and cause mitochondrial dysfunction and misfolding of α-syn; of these, oxidative stress is considered to be one of the primary causes of iron overload leading to PD.…”

Section: Introductionmentioning

confidence: 99%

“…Iron injection into the brain of animals also induced behavioural changes and symptoms of PD 10,11 . The iron accumulation in the SN via the deletion of the Iron regulatory protein 2 exacerbated dopaminergic neuron apoptosis and Parkinsonism symptoms 12 . High dietary iron increased the death of dopaminergic neuron, and reduced the content of dopamine in transgenic mice with overexpressing human A53T α‐syn 13 .…”

Section: Introductionmentioning

confidence: 99%

Iron‐inhibited autophagy via transcription factor ZFP27 in Parkinson's disease

Wang,

Wen,

Chen

et al. 2023

J Cellular Molecular Medi

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Parkinson's disease (PD) is a challenge because of the ageing of the population and the disease's complicated pathogenesis. Accumulating evidence showed that iron and autophagy were involved in PD. Nevertheless, the molecular mechanism and role of iron and autophagy in PD are not yet elucidated. In the present study, it was shown that PD mice had significant motor dysfunction, increased iron content, less dopamine neurons and more α‐synuclein accumulation in the substantia nigra. Meanwhile, PD mice treated with deferoxamine exhibited less iron content, relieved the dyskinesia and had a significant increase in dopamine neurons and a significant decrease in α‐synuclein. Autophagy induced by LC3 was inhibited in PD models with iron treatment. Following verification showed that iron aggregation restrained insulin‐like growth factor 2 (IGF2) and transcription factor zinc finger protein 27 (ZFP27) in PD models. In addition, LC3‐induced autophagy flux was reduced with ZFP27 knockdown. Furthermore, ZFP27 affected autophagy by regulating LC3 promoter activity. These data suggest that iron deposition inhibits IGF2 and ZFP27 to reduce LC3‐induced autophagy, and ultimately decrease dopamine neurons, accelerating PD progression. Our findings provide a novel insight that ZFP27‐mediated iron‐related autophagy and IGF2 may activate the downstream kinase gene to trigger autophagy in the PD model.

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“…On one hand, low levels of brain iron in adults are connected to restless legs syndrome (RLS) (Connor et al, 2003; O'Keeffe et al, 1994), cognitive decline (Bartzokis et al, 2011), and sleep disorders (Earley et al, 2006). On the other hand, excessive iron in the brain is causatively linked to many neurodegenerative disorders (Kim & Connor, 2020), such as Parkinson's disease (PD) (Ci et al, 2020; Wang et al, 2016), amyotrophic lateral sclerosis (Gajowiak et al, 2016), and Alzheimer's disease (AD) (Ayton et al, 2019; Liu et al, 2018). Thus, neurological health and proper functioning rely on the maintenance of iron homeostasis and requires tight regulation at the blood–brain barrier (BBB).…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Brain iron acquisition: An overview of homeostatic regulation and disease dysregulation

Baringer

Simpson

Connor

2023

Journal of Neurochemistry

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Brain iron homeostasis is crucial for neurological health, with pathological fluctuations in brain iron levels associated with a variety of neurological disorders. Low levels are connected to cognitive impairment and restless legs syndrome, while high levels are connected to Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. Given the detrimental effects unrestricted iron can have, regulated entry into the brain via transferrin and H‐ferritin is critical. Endothelial cells of the blood–brain barrier are the site of iron transport regulation. The movement of iron through endothelial cells into the brain can be divided into three distinct processes: uptake, transcytosis, and release. Each process possesses external and internal influences on the regulation at each stage. This review discusses the mechanisms of iron uptake, transcytosis, and release at the blood–brain barrier, as well as the elements that contribute to regulation. Additionally, we explore the dysregulation of brain iron in Alzheimer's disease, Parkinson's disease, and restless legs syndrome.

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Iron overload induced by IRP2 gene knockout aggravates symptoms of Parkinson's disease

Cited by 15 publications

References 38 publications

Ferritin: An Inflammatory Player Keeping Iron at the Core of Pathogen-Host Interactions

Ferritin: An Inflammatory Player Keeping Iron at the Core of Pathogen-Host Interactions

Iron‐inhibited autophagy via transcription factor ZFP27 in Parkinson's disease

Brain iron acquisition: An overview of homeostatic regulation and disease dysregulation

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