The Emerging Roles of Ferroptosis in Huntington’s Disease

Mi, Yajing; Gao, Xingchun; Xu, Hao; Cui, Yuanyuan; Zhang, Yuelin; Gou, Xin

doi:10.1007/s12017-018-8518-6

Cited by 70 publications

(45 citation statements)

References 93 publications

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“…Nevertheless, PCBP1, an iron chaperon for ferritin, may be involved in ferroptosis in HD. Ferroptosis is a new form of cell death caused by intracellular iron and reactive oxygen species accumulation, and ferroptosis is associated with HD pathophysiology . Further, in the present study, we observed colocalization of PCBP1 with INIs in HD patients.…”

Section: Discussionsupporting

confidence: 73%

Expanded polyglutamine impairs normal nuclear distribution of fused in sarcoma and poly (rC)‐binding protein 1 in Huntington's disease

et al. 2019

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Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Immunohistochemical studies using the 1C2 antibody for polyglutamine expansion have detected characteristic intranuclear inclusions (INIs) in affected neurons in HD. Further, in vitro and mouse models of HD have shown that the INIs recruit several proteins relating to RNA splicing and translation. In the present study, we immunohistochemically investigated the association of INIs with various heterogeneous nuclear ribonucleoproteins in the cerebral cortex of four autopsy cases of HD. Fused in sarcoma (FUS) was colocalized with 1C2‐positive nuclear inclusions in all examined cases. Localization of poly (rC)‐binding protein 1 (PCBP1) in 1C2‐positive nuclear inclusions was also observed. Double immunofluorescence revealed complete or partial loss of the normal, diffuse nuclear distribution of FUS or PCBP1 in neurons with 1C2‐positive nuclear inclusions. This maldistribution of FUS in cortical neurons suggests a severe disturbance of messenger RNA processing, which may be a common pathogenetic mechanism of FUS‐related familial amyotrophic lateral sclerosis.

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Section: Discussionsupporting

confidence: 73%

Expanded polyglutamine impairs normal nuclear distribution of fused in sarcoma and poly (rC)‐binding protein 1 in Huntington's disease

et al. 2019

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“…The blood-brain barrier (BBB) ingests iron through transferrin on brain capillary endothelial cells, and then transports it into the cerebral cytoplasm through astrocytes or through divalent cation-binding protein (DMT1) and maintains iron an approximately saturated steady state in the brain (Belaidi and Bush, 2016), thereby maintaining the normal physiological function of the nervous system. After the formal concept of ferroptosis publishing, the researchers began to believe that ferroptosis is the main driver of neuronal death in diseases such as PD, AD, and HD (Guiney et al, 2017;Morris et al, 2018;Mi et al, 2019). In animal models of aging and neurodegenerative diseases and human anatomy studies, iron levels in the brain were found to rise to varying degrees, and it was concluded that this increase may lead to age-dependent ferroptosis (Belaidi and Bush, 2016;Buijs et al, 2017).…”

Section: Research Progress On Ferroptosis and Neurodegenerative Diseasesmentioning

confidence: 99%

“…In recent years, with the rapid development of ferroptosis-related research in many fields, it has made a great impact on the fields of cancer therapy, neurodegenerative diseases, ischemia and reperfusion, etc. After the formal concept of ferroptosis, the researchers began to believe that ferroptosis is the main driver of neuronal death in diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD) (Guiney et al, 2017;Morris et al, 2018;Mi et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Nrf2 and Ferroptosis: A New Research Direction for Neurodegenerative Diseases

2020

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“…Also, it has been demonstrated that ferroptosis is an important cell death pathway for dopaminergic neurons that is regulated by protein kinase C in PD, and that autophagy contributes to ferroptosis by the degradation of ferritin . Ferroptosis has also been considered as a novel therapeutic target for Friedreich's Ataxia, AD, and HD . Since the discovery of the ferroptosis, iron, and ROS have been increasingly acknowledged as crucial initiators and mediators of cell death in a variety of organisms and pathological situations.…”

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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The Emerging Roles of Ferroptosis in Huntington’s Disease

Cited by 70 publications

References 93 publications

Expanded polyglutamine impairs normal nuclear distribution of fused in sarcoma and poly (rC)‐binding protein 1 in Huntington's disease

Expanded polyglutamine impairs normal nuclear distribution of fused in sarcoma and poly (rC)‐binding protein 1 in Huntington's disease

Nrf2 and Ferroptosis: A New Research Direction for Neurodegenerative Diseases

Hepcidin and its therapeutic potential in neurodegenerative disorders

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