Apoferritin improves motor deficits in MPTP-treated mice by regulating brain iron metabolism and ferroptosis

Song, Lingling; Xiao, Zhixin; Zhang, Na; Yu, Xiao‐Qi; Cui, Wei; Xie, Junxia; Xu, Huamin

doi:10.1016/j.isci.2021.102431

Cited by 45 publications

(27 citation statements)

References 53 publications

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“…Human brain imaging studies have shown that DFP decreases brain iron levels, alters cerebrospinal fluid ferritin, and mitigates dyskinesia ( Martin-Bastida et al, 2017 ). Similarly, both the blockage of ferritin degradation by ferritinophagy inhibitors chloroquine and bafilomycin A1 and the application of an iron-free form of ferritin, apoferritin, have been reported to chelate excess iron to protect DA neurons against PD ( Tian et al, 2020 ; Song et al, 2021 ). Moreover, NADPH oxidase inhibitor apocynin was also found to inhibit iron accumulation and lipid peroxidation, therefore ameliorating dopaminergic neurodegeneration and motor function abnormality in PD mice ( Hou et al, 2019 ).…”

Section: Emerging Links Of Ferroptosis To Neurodegenerative Diseasesmentioning

confidence: 99%

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Sun

Xia

Basnet

et al. 2022

Front. Aging Neurosci.

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Neurodegenerative diseases are a diverse class of diseases attributed to chronic progressive neuronal degeneration and synaptic loss in the brain and/or spinal cord, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis. The pathogenesis of neurodegenerative diseases is complex and diverse, often involving mitochondrial dysfunction, neuroinflammation, and epigenetic changes. However, the pathogenesis of neurodegenerative diseases has not been fully elucidated. Recently, accumulating evidence revealed that ferroptosis, a newly discovered iron-dependent and lipid peroxidation-driven type of programmed cell death, provides another explanation for the occurrence and progression of neurodegenerative diseases. Here, we provide an overview of the process and regulation mechanisms of ferroptosis, and summarize current research progresses that support the contribution of ferroptosis to the pathogenesis of neurodegenerative diseases. A comprehensive understanding of the emerging roles of ferroptosis in neurodegenerative diseases will shed light on the development of novel therapeutic technologies and strategies for slowing down the progression of these diseases.

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Section: Emerging Links Of Ferroptosis To Neurodegenerative Diseasesmentioning

confidence: 99%

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Sun

Xia

Basnet

et al. 2022

Front. Aging Neurosci.

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“…Moreover, inhibition of the production of microglial proinflammatory cytokines and lipid peroxidation by knocking down acyl-CoA synthetase long-chain family member 4 (ACSL4) in an ischemic stroke model prevented ferroptosis in neurons [68]. Similar neuroprotective effects on ACSL4 were observed in the MPTP-induced PD model [69].…”

Section: Microgliamentioning

confidence: 76%

Ferroptosis in Parkinson’s disease: glia–neuron crosstalk

Wang

Yuan

et al. 2022

Trends in Molecular Medicine

149

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“…Our previous study demonstrates that the expression of divalent metal transporter 1 (DMT1) is increased with excessive iron deposition in injured spinal cord, and reduced DMT1 expression decreases iron accumulation with the treatment of deferoxamine [ 54 ]. Further evidence indicates that the upregulation of transferrin receptor 1 (TfR1) reduces iron accumulation with the application of apoferritin [ 55 ]. Hence, it is reasonable to believe that DPX reduces iron accumulation at perihematomal site that might ascribe to mediating the expression of DMT1 and TfR1 that is going to be investigated in our future research.…”

Section: Discussionmentioning

confidence: 99%

Dexpramipexole Attenuates White Matter Injury to Facilitate Locomotion and Motor Coordination Recovery via Reducing Ferroptosis after Intracerebral Hemorrhage

Wang

Zhang

Zhong

et al. 2022

Oxidative Medicine and Cellular Longevity

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Deciphering the factors causing damage to white matter fiber bundles and exploring new strategies to alleviate white matter injury (WMI) is a promising treatment to improve neurological impairments after intracerebral hemorrhage (ICH). Ferroptosis usually occurs at perihematomal region and contributes to neuronal death due to reactive oxygen species (ROS) production. Dexpramipexole (DPX) easily crosses the blood brain barrier (BBB) and exerts antioxidative properties by reducing ROS production, while the role of DPX in ferroptosis after ICH remains elusive. Here, our results indicated that ferroptosis played a significant role in WMI resulting from iron and ROS accumulation around hematoma. Further evidence demonstrated that the administration of DPX decreased iron and ROS deposition to inhibit ferroptosis at perihematomal site. With the inhibition of ferroptosis, WMI was alleviated at perihematomal site, thereafter promoting locomotion and motor coordination recovery in mice after ICH. Subsequently, the results showcased that the expression of glutathione peroxidase 4 (GPX4) and ferroptosis suppressing protein 1 (FSP1) was upregulated with the administration of DPX. Collectively, the present study uncovers the underlying mechanism and elucidates the therapeutic effect of DPX on ICH, and even in other central nervous system (CNS) diseases with the presence of ferroptosis.

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Apoferritin improves motor deficits in MPTP-treated mice by regulating brain iron metabolism and ferroptosis

Abstract: HighlightsApoferritin improved MPTP-induced motor deficits.Apoferritin rescued dopaminergic neurodegeneration in the SN of MPTP-treated mice. Apoferritin inhibited MPTP-induced iron aggregation.Apoferritin prevented MPTP-induced ferroptosis by regulation of ACSL4 and FSP1.

Cited by 45 publications

References 53 publications

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Ferroptosis in Parkinson’s disease: glia–neuron crosstalk

Dexpramipexole Attenuates White Matter Injury to Facilitate Locomotion and Motor Coordination Recovery via Reducing Ferroptosis after Intracerebral Hemorrhage

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