Iron induces two distinct Ca2+ signalling cascades in astrocytes

Guan, Wenzheng; Xia, Maosheng; Ji, Ming; Chen, Beina; Li, Shuai; Zhang, Manman; Liang, Shangdong; Chen, Binjie; Gong, Wenliang; Dong, Chengyi; Wen, Gehua; Zhan, Xiaoni; Zhang, Dianjun; Li, Xinyu; Zhou, Yuefei; Guan, Dawei; Verkhratsky, Alexei

doi:10.1038/s42003-021-02060-x

Cited by 26 publications

(13 citation statements)

References 83 publications

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“…Their expression of the Fc gamma receptor (FcγRI), which binds to the Fc component of the immunoglobulin IgG (56), may facilitate cell uptake of the antibody-PMO conjugate. Some experimental evidence also suggests TfR expression on astrocytic cell membrane (57)(58)(59).…”

Section: Discussionmentioning

confidence: 97%

Antibody-oligonucleotide conjugate achieves CNS delivery in animal models for spinal muscular atrophy

Hammond¹,

Abendroth²,

Goli³

et al. 2022

JCI Insight

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Antisense oligonucleotides (ASOs) have emerged as one of the most innovative new genetic drug modalities. However, their high molecular weight limits their bioavailability for otherwise treatable neurological disorders. We investigated conjugation of ASOs to an antibody against the murine transferrin receptor (TfR), 8D3130, and evaluated it via systemic administration in mouse models of the neurodegenerative disease, spinal muscular atrophy (SMA). SMA, like several other neurological and neuromuscular diseases, is treatable with single-stranded ASOs that modulate splicing of the survival motor neuron 2 (SMN2) gene.Administration of 8D3130-ASO conjugate resulted in elevated levels of bioavailability to the brain. Additionally, 8D3130-ASO yielded therapeutic levels of SMN2 splicing in the central nervous system of adult hSMN2 transgenic mice which resulted in extended survival of a severely affected SMA mouse model. Systemic delivery of nucleic acid therapies with brain targeting antibodies offers powerful translational potential for future treatments of neuromuscular and neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 97%

Antibody-oligonucleotide conjugate achieves CNS delivery in animal models for spinal muscular atrophy

Hammond¹,

Abendroth²,

Goli³

et al. 2022

JCI Insight

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“…The labelled cells were sorted and collected using the BD FACSAria Cell Sorting System (San Jose, CA) [17,24]. The purity of sorted astrocytes was ascertained by detecting mRNA of the cell-specific marker as described previously [13,23,25,26].…”

Section: Fluorescence-activated Cell Sorter (Facs)mentioning

confidence: 99%

A novel murine model of mania

Chen

Zhang

et al. 2023

Mol Psychiatry

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Neuropathological mechanisms of manic syndrome or manic episodes in bipolar disorder remain poorly characterised, as the research progress is severely limited by the paucity of appropriate animal models. Here we developed a novel mania mice model by combining a series of chronic unpredictable rhythm disturbances (CURD), which include disruption of circadian rhythm, sleep deprivation, exposure to cone light, with subsequent interference of followed spotlight, stroboscopic illumination, high-temperature stress, noise disturbance and foot shock. Multiple behavioural and cell biology tests comparing the CURD-model with healthy controls and depressed mice were deployed to validate the model. The manic mice were also tested for the pharmacological effects of various medicinal agents used for treating mania. Finally, we compared plasma indicators of the CURD-model mice and the patients with the manic syndrome. The CURD protocol produced a phenotype replicating manic syndrome. Mice exposed to CURD presented manic behaviours similar to that observed in the amphetamine manic model. These behaviours were distinct from depressive-like behaviours recorded in mice treated with a depression-inducing protocol of chronic unpredictable mild restraint (CUMR). Functional and molecular indicators in the CURD mania model showed multiple similarities with patients with manic syndrome. Treatment with LiCl and valproic acid resulted in behavioural improvements and recovery of molecular indicators. A novel manic mice model induced by environmental stressors and free from genetic or pharmacological interventions is a valuable tool for research into pathological mechanisms of mania.

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“…Fe 2+ is oxidized to Fe 3+ by ceruloplasmin (CP) and hephaestin (HP), and Fe 3+ combines with transferrin (Tf) to be transported in the blood [ 25 ]. Tf-Fe 3+ attaches to the transferrin receptor (TfR) on the cell membrane and then internalizes to the cell as endosomes [ 26 , 27 ]. Fe 3+ is released and reduced to Fe 2+ by 6-transmembrane epithelial antigen of the prostate 3 (STEAP3) in a variety of cells; then, Fe 2+ enters the cytoplasm via DMT1 on the endosomal membrane [ 28 , 29 ].…”

Section: Molecular Mechanisms Of Ferroptosismentioning

confidence: 99%

Ferroptosis and Its Potential Role in Glioma: From Molecular Mechanisms to Therapeutic Opportunities

et al. 2022

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Glioma is the most common intracranial malignant tumor, and the current main standard treatment option is a combination of tumor surgical resection, chemotherapy and radiotherapy. Due to the terribly poor five-year survival rate of patients with gliomas and the high recurrence rate of gliomas, some new and efficient therapeutic strategies are expected. Recently, ferroptosis, as a new form of cell death, has played a significant role in the treatment of gliomas. Specifically, studies have revealed key processes of ferroptosis, including iron overload in cells, occurrence of lipid peroxidation, inactivation of cysteine/glutathione antiporter system Xc− (xCT) and glutathione peroxidase 4 (GPX4). In the present review, we summarized the molecular mechanisms of ferroptosis and introduced the application and challenges of ferroptosis in the development and treatment of gliomas. Moreover, we highlighted the therapeutic opportunities of manipulating ferroptosis to improve glioma treatments, which may improve the clinical outcome.

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Iron induces two distinct Ca2+ signalling cascades in astrocytes

Cited by 26 publications

References 83 publications

Antibody-oligonucleotide conjugate achieves CNS delivery in animal models for spinal muscular atrophy

Antibody-oligonucleotide conjugate achieves CNS delivery in animal models for spinal muscular atrophy

A novel murine model of mania

Ferroptosis and Its Potential Role in Glioma: From Molecular Mechanisms to Therapeutic Opportunities

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