Ferroptosis was more initial in cell death caused by iron overload and its underlying mechanism in Parkinson's disease

Zhang, Pei; Chen, Ling; Zhao, Qiqi; Du, Xixun; Bi, Minghong; Li, Yong; Jiao, Qian; Jiang, Hong

doi:10.1016/j.freeradbiomed.2020.03.015

Cited by 138 publications

(80 citation statements)

References 42 publications

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“…Maged1 interacts with p75NTR, resulting in caspase activation and cell death through a JNK-dependent mitochondrial pathway [27]. In addition, Maged1 is reported to up-regulate p53 transcriptional activity [28], which is a well-known regulator of cell apoptosis and ferroptosis involved in PD [29,30]. Thus, Maged1 may play a proapoptotic role through interacting with p75NTR or regulating the p53-signaling pathway in the progression of PD.…”

Section: Discussionmentioning

confidence: 99%

The Deficiency of Maged1 Attenuates Parkinson's Disease Progression by Inhibiting Apoptosis and Enhancing Autophagy in Mice

Wang¹,

You²,

Ye³

et al. 2020

Preprint

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Background: Melanoma-associated antigen D1 (Maged1) is expressed in most adult tissues, predominantly in the brain, and has critical functions in the central nervous system in both developmental and adult stages. Loss of Maged1 in mice has been linked to depression, cognitive disorder, circadian rhythm, and drug addiction. However, the role of Maged1 in Parkinson’s disease (PD) remains unclear.Methods: Immunostaining was performed to investigate the expression of Maged1 in the samples from mice and human. To make the acute mice model of PD, C57BL/6 mice and Maged1 knockout mice were injected with 20 mg/kg 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) four times, every 2-hour intervals. SY5Y cells were treated by 200 μM 1-Methyl-4-phenylpyridinium iodide (MPP+). To examine motor balance and coordination, the rotarod test and pole test were used. Then we further investigated the role of Maged1 deficiency in DA neurons by high-performance liquid chromatography, immunohistochemistry, western blot, CCK8 assay, and gene transfection in vivo or in vitro.Results: Maged1 was expressed in DA neurons of samples from mice and human. And the expression of Maged1 was time-dependently upregulated by the treatment with MPTP or MPP+ in vivo or in vitro. Knockout of Maged1 in mice partly rescued the motor deficits and the reduced levels of striatal dopamine and its metabolites by MPTP treatment. Moreover, Maged1 deficiency protected primary DA neurons and differentiated ReNcell VM cells from MPP+ toxicity. Furthermore, along with the overexpression or downregulation of Maged1 in cultured SH-SY5Y cells, the reduced the cell viability by MPP+ treatment was relatively aggerated or attenuated. The effect of Maged1 deficiency may be attributed to the upregulated Akt signaling pathway and the downregulated mTOR signaling pathway, which further attenuated the MPTP or MPP+ -induced cell apoptosis and impairment of autophagy. Consistent with the above data, the degeneration of midbrain and striatum among 15-m Maged1 knockout mice was relatively mild compared to those in 15-m wild-type mice under physiological conditions.Conclusions: Maged1 deficiency-mediated apoptosis inhibition and autophagy enhancement may be a potential pro-survival mechanism during the progression of PD.

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Section: Discussionmentioning

confidence: 99%

The Deficiency of Maged1 Attenuates Parkinson's Disease Progression by Inhibiting Apoptosis and Enhancing Autophagy in Mice

Wang¹,

You²,

Ye³

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…This indicated that a lower DFP dose was safe with a risk for reversible neutropenia of 1-3% (Devos et al, 2014). Moreover, a study by Zhang et al (2020) reported that ferroptosis occurred at a relatively low ferric citrate concentration, while apoptosis occurred with an increase in the iron dose. This is indicative of the role of early death in PD and shows that ferroptosis can result in apoptosis caused by iron overload.…”

Section: Iron Chelators In Pdmentioning

confidence: 93%

“…This is indicative of the role of early death in PD and shows that ferroptosis can result in apoptosis caused by iron overload. Furthermore, the specific ferroptosis inhibitor Fer-1 and the iron chelator DFO inhibit iron-induced cell death and apoptosis in the early PD stages (Zhang et al, 2020). In addition, a recent study shows that in the rodent Parkinson's disease model, Clioquinol has the effect of an iron chelator.…”

Section: Iron Chelators In Pdmentioning

confidence: 99%

Ferroptosis in Neurological Diseases

Ren

Sun

Yan

et al. 2020

Front. Cell. Neurosci.

118

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Ferroptosis is mechanism for non-apoptotic, iron-dependent, oxidative cell death that is characterized by glutathione consumption and lipid peroxides accumulation. Ferroptosis is crucially involved in neurological diseases, including neurodegeneration, stroke and neurotrauma. This review provides detailed discussions of the ferroptosis mechanisms in these neurological diseases. Moreover, it summarizes recent drugs that target ferroptosis for neurological disease treatment. Furthermore, it compares the differences and relationships among the various cell death mechanisms involved in neurological diseases. Elucidating the ferroptosis role in the brain can improve the understanding of neurological disease mechanism and provide potential prevention and treatment interventions for acute and chronic neurological diseases.

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“…LUHMES (Lund's human mesencephalic cells) were exposed to controlled materials from fe-nm-SIM and 3D silk fibroin scaffolds for 2 weeks, in which the precipitation produced peroxides that deplete nutrients/antioxidants, leading to cellular dysfunction [27]. In addition to its ability to interact with neuromelatonin and affect neuron cells, Fe has recently been found to have a typical form of cell death dependent on iron called ferroptosis, which is characterized by the accumulation of lipid peroxidation products and ROS [28]. The aggregation-membrane interaction is the key to induce ferroptosis, which depends not only on the conformation structure of the aggregates but also on the oxidation state of the lipid membrane.…”

Section: Oxidative Stress and Pdmentioning

confidence: 99%

Oxidative Stress and Neuroinflammation Potentiate Each Other to Promote Progression of Dopamine Neurodegeneration

Zhu

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Parkinson’s disease (PD) is a chronic and complex disease of the central nervous system (CNS). Progressive loss of dopamine (DA) neurons in midbrain substantia nigra is considered to be the main cause of PD. The hallmark of PD pathology is the formation of Lewy bodies and the deposition of α-synuclein (α-syn). The mechanisms responsible for the progressive feature of DA neurodegeneration are not fully illustrated. Recently, oxidative stress and neuroinflammation have received extensive attention as two important entry points in the pathogenesis of PD. The occurrence of oxidative stress and neuroinflammation is usually derived from external influences or changes in internal environment, such as the accumulation of reactive oxygen species, exposure to a toxic environment, and the transformation of systemic inflammation. However, PD never results from a single independent factor and the simultaneous participation of oxidative stress and neuroinflammation contributed to PD development. Oxidative stress and neuroinflammation could potentiate each other to promote progression of PD. In this review, we briefly summarized the conditions of oxidative stress and neuroinflammation and the crosstalk between oxidative stress and neuroinflammation on the development of PD.

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Ferroptosis was more initial in cell death caused by iron overload and its underlying mechanism in Parkinson's disease

Cited by 138 publications

References 42 publications

The Deficiency of Maged1 Attenuates Parkinson's Disease Progression by Inhibiting Apoptosis and Enhancing Autophagy in Mice

The Deficiency of Maged1 Attenuates Parkinson's Disease Progression by Inhibiting Apoptosis and Enhancing Autophagy in Mice

Ferroptosis in Neurological Diseases

Oxidative Stress and Neuroinflammation Potentiate Each Other to Promote Progression of Dopamine Neurodegeneration

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