Neurotoxic A1 astrocytes promote neuronal ferroptosis via CXCL10/CXCR3 axis in epilepsy

Article Pharmacology & Pharmacy

beta-elemene relieves neuropathic pain in mice through the regulation on C-X-C motif chemokine receptor 3 and GABAA receptor

Yi Dai et al.

Summary: The study found that beta-elemene can alleviate neuropathic pain in mice by inhibiting CXCR3 and upregulating GABAA receptor.

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY (2022)

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Article Biochemistry & Molecular Biology

Characterization of a patient-derived variant of GPX4 for precision therapy

Hengrui Liu et al.

Summary: A homozygous point mutation in the GPX4 gene, resulting in an R152H coding mutation, was identified in patients with Sedaghatian-type spondylometaphyseal dysplasia. The missense variant destabilized a critical loop in the enzyme, disrupting the active site and causing a loss of enzymatic function. Therapeutic treatments targeting the impaired R152H GPX4 activity were identified, including selenium supplementation, selective antioxidants, and a deuterated polyunsaturated fatty acid.

NATURE CHEMICAL BIOLOGY (2022)

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Review Biotechnology & Applied Microbiology

Function and therapeutic value of astrocytes in neurological diseases

Hong-Gyun Lee et al.

Summary: This review discusses astrocytes, a type of glial cell that is involved in various neurological diseases. Astrocytes regulate important processes in the central nervous system, such as glutamate and ion homeostasis, cholesterol and sphingolipid metabolism, and response to environmental factors. The review highlights the potential of targeting astrocytes for therapeutic intervention, including manipulating their metabolism and targeting transporters and receptors on astrocytes. The review also proposes a new nomenclature for astrocyte subsets to better understand their roles in neurological diseases.

NATURE REVIEWS DRUG DISCOVERY (2022)

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Article Multidisciplinary Sciences

TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen-induced arthritis mouse models

Jiao Wu et al.

Summary: In this study, the authors use a mouse model of rheumatoid arthritis (RA) and single-cell RNA sequencing to show that inducing ferroptosis and suppressing TNF signaling can reduce the number of fibroblasts in the synovium and improve experimental arthritis. They further identify two groups of fibroblasts with distinct susceptibility to ferroptosis and show that TNF signaling protects fibroblasts from ferroptosis through promoting cystine uptake and glutathione biosynthesis. Finally, the combination of low-dose ferroptosis inducer and TNF antagonist attenuates arthritis progression in the mouse model.

NATURE COMMUNICATIONS (2022)

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Article Medicine, General & Internal

Contribution of ferroptosis and GPX4's dual functions to osteoarthritis progression

Yu Miao et al.

Summary: This study demonstrated the presence of ferroptosis in osteoarthritis (OA) and identified glutathione peroxidase 4 (GPX4) as a crucial regulator of OA. By downregulating GPX4 expression, the crosstalk between ferroptosis and extracellular matrix degradation pathways influenced the progression of OA.

EBIOMEDICINE (2022)

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Review Medicine, Research & Experimental

Mechanism of cell death pathways in status epilepticus and related therapeutic agents

Ke Du et al.

Summary: This article reviews the mechanisms of neuronal death related to status epilepticus (SE) and potential treatment methods that target neuronal death.

BIOMEDICINE & PHARMACOTHERAPY (2022)

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Article Oncology

CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4

Peng Liao et al.

Summary: T cell-derived interferon gamma (IFN γ) in combination with arachidonic acid (AA) induces immunogenic tumor ferroptosis, serving as a mechanism for CD8(+) T cell-mediated tumor killing. This process involves IFN γ stimulation of ACSL4 and alteration of tumor cell lipid pattern.

CANCER CELL (2022)

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Article Pharmacology & Pharmacy

Critical involvement of lysyl oxidase in seizure- induced neuronal damage through ERK-Alox5-dependent ferroptosis and its therapeutic implications

Xiaoyuan Mao et al.

Summary: Recent insights suggest the important roles of lysyl oxidase (LysOX) in various neurological diseases, but the molecular mechanisms are still unclear. This study reveals the regulatory role of LysOX in seizure-induced ferroptotic cell death of neurons and uncovers its association with the ERK-Alox5 pathway.

ACTA PHARMACEUTICA SINICA B (2022)

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Article Biochemistry & Molecular Biology

SLC7A11, a Potential Therapeutic Target Through Induced Ferroptosis in Colon Adenocarcinoma

Xin Cheng et al.

Summary: SLC7A11, which is overexpressed in colon adenocarcinoma (COAD), is strongly correlated with the infiltration levels of immune cells and lymphocyte markers. Additionally, five hub genes co-expressed with SLC7A11 that induce ferroptosis were identified, suggesting potential therapeutic targets for COAD treatment.

FRONTIERS IN MOLECULAR BIOSCIENCES (2022)

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Review Biochemistry & Molecular Biology

Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications

Brent R. Stockwell

Summary: This review describes the key regulators of ferroptosis and provides an overview of metabolism, ROS biology, and iron biology. Additionally, it highlights the important concepts and unanswered questions in the field of ferroptosis. The future holds promise for further breakthroughs in understanding the mechanisms of ferroptosis and utilizing it for therapeutic purposes.

CELL (2022)

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Article Endocrinology & Metabolism

Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo

Michael P. Murphy et al.

Summary: This article discusses the important roles of reactive oxygen species (ROS) in health and disease, and proposes guidelines and best practices for the nomenclature and assessment of ROS, oxidative reactions, and oxidative damage in cells, tissues, and in vivo.

NATURE METABOLISM (2022)

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Review Cell Biology

Ferroptosis: molecular mechanisms and health implications

Daolin Tang et al.

Summary: Cell death can be executed through different subroutines, such as ferroptosis which is an iron-dependent form of non-apoptotic cell death. Ferroptosis can occur through two major pathways, driven by redox imbalance and abnormal expression of redox-active enzymes. The process is precisely regulated at multiple levels, with the transcription factor NFE2L2 playing a central role in anti-ferroptotic defense.

CELL RESEARCH (2021)

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Article Biochemistry & Molecular Biology

Protective role of microglial HO-1 blockade in aging: Implication of iron metabolism

Cristina Fernandez-Mendivil et al.

Summary: The study revealed that overexpression of HO-1 in microglial cells in aged mice leads to neurotoxic iron accumulation, oxidative stress, and cognitive decline. Inhibiting HO-1 or using an iron chelator can prevent these issues, providing new insights for treating age-related neurodegenerative diseases.

REDOX BIOLOGY (2021)

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Article Cell Biology

CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability

Xingzhe Ma et al.

Summary: Understanding the mechanisms of how T cells become dysfunctional in a tumor microenvironment is crucial for cancer immunotherapy. This study found that CD36 expression in tumor-infiltrating CD8(+) T cells, induced by TME cholesterol, is associated with tumor progression and poor survival, and that genetic ablation of Cd36 in these T cells leads to enhanced tumor eradication. Targeting CD36 or inhibiting ferroptosis could restore T cell function and enhance antitumor efficacy, especially in combination with anti-PD-1 antibodies.

CELL METABOLISM (2021)

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Article Multidisciplinary Sciences

Neurotoxic reactive astrocytes induce cell death via saturated lipids

Kevin A. Guttenplan et al.

Summary: Astrocytes respond to diseases and injuries in the central nervous system by releasing long-chain saturated fatty acids contained in lipoparticles, leading to the death of neurons and mature oligodendrocytes. The elimination of saturated lipids produced by astrocytes can mitigate astrocyte-induced toxicity, suggesting a mechanism by which astrocytes kill cells in the central nervous system.

NATURE (2021)

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Article Immunology

The effect of dipeptidyl peptidase IV on disease-associated microglia phenotypic transformation in epilepsy

Zhicheng Zheng et al.

Summary: The study revealed that DPP4 is involved in DAM conversion and epilepsy, and treatment with DPP4 inhibitor sitagliptin can alleviate epilepsy and promote DAM phenotypic transformation, resulting in enhanced morphological features and functions of microglia.

JOURNAL OF NEUROINFLAMMATION (2021)

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Article Multidisciplinary Sciences

DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer

Chao Mao et al.

Summary: The study reveals the mechanism of ferroptosis induced by inhibiting GPX4 in cancer cells, as well as the potential pathways to enhance or inhibit ferroptosis by intervening in relevant metabolic pathways. Therapeutic strategies targeting different levels of GPX4 expression could be a promising new approach for cancer treatment.

NATURE (2021)

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Article Multidisciplinary Sciences

Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients

Silvia Yumi Bando et al.

Summary: By adopting a systems biology approach and analyzing clinical, histopathological, and transcriptomic data, we identified transcriptional modules highly correlated with age of disease onset, cognitive dysfunctions, and granule cell alterations in RMTLE patients. Furthermore, we discovered 15 genes with high gene significance values that could potentially serve as novel biomarkers and therapeutic targets in RMTLE. This study sheds light on the pathophysiology of RMTLE and opens avenues for further investigations.

SCIENTIFIC REPORTS (2021)

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Review Biochemistry & Molecular Biology

Molecular mechanisms of cell death in neurological diseases

Diane Moujalled et al.

Summary: Cell death plays a critical role in the pathogenesis of neurological diseases and brain cancers, with abnormal activation of PCD pathways being a common feature. Controlling PCD pathways may be a key component of future therapeutic strategies for these diseases.

CELL DEATH AND DIFFERENTIATION (2021)

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Review Neurosciences

Ferroptosis and Its Role in Epilepsy

Yuxiang Cai et al.

Summary: Epilepsy is a common symptom of various neurological disorders, and the role of ferroptosis in epilepsy pathogenesis and neuronal damage is being increasingly recognized.

FRONTIERS IN CELLULAR NEUROSCIENCE (2021)

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Article Biochemistry & Molecular Biology

Imbalance of Systemic Redox Biomarkers in Children with Epilepsy: Role of Ferroptosis

Sara Petrillo et al.

Summary: This study found marked dysregulation of ferroptosis biomarkers in blood of children with epilepsy, including increased 4-HNE, decreased GSH levels, partial GPX4 inactivation, and increased NOX2. NRF2 activation in patients was not enough to counterbalance ferroptosis-mediated oxidative damage. The identification of useful biomarkers and the development of innovative drugs targeting the ferroptosis signaling axis may represent a promising strategy for new anti-seizure medications.

ANTIOXIDANTS (2021)

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Editorial Material Biochemistry & Molecular Biology