Ferroptosis in infection, inflammation, and immunity

The Journal of Experimental Medicine, Год журнала: 2021, Номер 218(6)

Опубликована: Май 12, 2021

Ferroptosis is a type of regulated necrosis that triggered by combination iron toxicity, lipid peroxidation, and plasma membrane damage. The upstream inducers ferroptosis can be divided into two categories (biological versus chemical) activate major pathways (the extrinsic/transporter the intrinsic/enzymatic pathways). Excessive or deficient ferroptotic cell death implicated in growing list physiological pathophysiological processes, coupled to dysregulated immune response. This review focuses on new discoveries related how cells their spilled contents shape innate adaptive immunity health disease. Understanding immunological characteristics activity not only illuminates an intersection between but may also lead development novel treatment approaches for immunopathological diseases.

Язык: Английский

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Molecular mechanisms of cell death in neurological diseases

Cell Death and Differentiation, Год журнала: 2021, Номер 28(7), С. 2029 - 2044

Опубликована: Июнь 7, 2021

Tightly orchestrated programmed cell death (PCD) signalling events occur during normal neuronal development in a spatially and temporally restricted manner to establish the neural architecture shaping CNS. Abnormalities PCD cascades, such as apoptosis, necroptosis, pyroptosis, ferroptosis, associated with autophagy well unprogrammed necrosis can be observed pathogenesis of various neurological diseases. These deaths activated response forms cellular stress (exerted by intracellular or extracellular stimuli) inflammatory processes. Aberrant activation pathways is common feature neurodegenerative diseases, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's Huntington's resulting unwanted loss cells function. Conversely, inactivation thought contribute brain cancers impact their therapy. For many diseases current treatment strategies have only modest effect, engendering need for investigations into origins these With displaying aberrations pathways, it appears that agents either inhibit induce may critical components future therapeutic strategies. The therapies will guided preclinical studies animal models faithfully mimic human disease. In this review, we briefly describe processes roles they play contributing tumorigenesis brain. We also discuss interplay between distinct cascades disease pharmacological targeting key players progressed through clinical trials.

Язык: Английский

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Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Дек. 8, 2022

Abstract Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death (RCD), is important for various activities, including clearance aberrant cells. Thus, RCD pathways represented by apoptosis have increased in importance as a target development cancer medications recent years. However, because tumor show avoidance apoptosis, which causes treatment resistance recurrence, numerous studies been devoted alternative mortality processes, namely necroptosis, pyroptosis, ferroptosis, cuproptosis; these modalities extensively studied shown be crucial therapy effectiveness. Furthermore, evidence suggests that undergoing may alter immunogenicity microenvironment (TME) some extent, rendering it more suitable inhibiting progression metastasis. In addition, other components TME undergo abovementioned forms induce immune attacks on cells, resulting enhanced antitumor responses. Hence, this review discusses molecular processes features cuproptosis effects novel proliferation Importantly, introduces complex affect biology. It also summarizes potential agents nanoparticles or inhibit their therapeutic based from vivo vitro reports clinical trials inducers evaluated treatments patients. Lastly, we summarized impact modulating drug advantages adding modulators over conventional treatments.

Язык: Английский

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Neutrophils in cancer carcinogenesis and metastasis

Journal of Hematology & Oncology, Год журнала: 2021, Номер 14(1)

Опубликована: Окт. 21, 2021

Abstract In recent years, neutrophils have attracted increasing attention because of their cancer-promoting effects. An elevated neutrophil-to-lymphocyte ratio is considered a prognostic indicator for patients with cancer. Neutrophils are no longer regarded as innate immune cells single function, let alone bystanders in the pathological process Their diversity and plasticity being increasingly recognized. This review summarizes previous studies assessing roles mechanisms cancer initiation, progression, metastasis relapse. Although findings controversial, fact that play dual role promoting suppressing undeniable. The allows them to adapt different microenvironments exert effects on Given from our own research, we propose reasonable hypothesis may be reprogrammed into state microenvironment. new perspective indicates neutrophil reprogramming course treatment problem worthy attention. Preventing or reversing potential strategy adjuvant therapy.

Язык: Английский

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Organelle-specific regulation of ferroptosis

Cell Death and Differentiation, Год журнала: 2021, Номер 28(10), С. 2843 - 2856

Опубликована: Авг. 31, 2021

Язык: Английский

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ACSL family: The regulatory mechanisms and therapeutic implications in cancer

European Journal of Pharmacology, Год журнала: 2021, Номер 909, С. 174397 - 174397

Опубликована: Июль 29, 2021

Язык: Английский

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Baicalin Prevents Myocardial Ischemia/Reperfusion Injury Through Inhibiting ACSL4 Mediated Ferroptosis

Frontiers in Pharmacology, Год журнала: 2021, Номер 12

Опубликована: Апрель 14, 2021

Baicalin is a natural flavonoid glycoside that confers protection against myocardial ischemia/reperfusion (I/R) injury. However, its mechanism has not been fully understood. This study focused on elucidating the role of ferroptosis in baicalin-generated protective effects injury by using I/R rat model and oxygen–glucose deprivation/reoxygenation (OGD/R) H9c2 cells. Our results show baicalin improved challenge–induced ST segment elevation, coronary flow (CF), left ventricular systolic pressure , infarct area, pathological changes prevented OGD/R-triggered cell viability loss. In addition, enhanced lipid peroxidation significant iron accumulation along with activated transferrin receptor protein 1 (TfR1) signal nuclear coactivator 4 (NCOA4)-medicated ferritinophagy were observed vivo vitro models, which reversed treatment. Furthermore, acyl-CoA synthetase long-chain family member (ACSL4) overexpression compromised effect Taken together, our findings suggest prevents via suppressing ACSL4-controlled ferroptosis. provides novel target for prevention

Язык: Английский

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Macrophages and microglia: the cerberus of glioblastoma

Acta Neuropathologica Communications, Год журнала: 2021, Номер 9(1)

Опубликована: Март 25, 2021

Abstract Glioblastoma (GBM) is the most aggressive and deadliest of primary brain tumors, characterized by malignant growth, invasion into parenchyma, resistance to therapy. GBM a heterogeneous disease high degrees both inter- intra-tumor heterogeneity. Another layer complexity arises from unique microenvironment in which develops grows. The consists neoplastic non-neoplastic cells. abundant cells are those innate immune system, called tumor-associated macrophages (TAMs). TAMs constitute up 40% tumor mass consist brain-resident microglia bone marrow-derived myeloid periphery. Although genetically stable, can change their expression profiles based upon signals that they receive cells; therefore, heterogeneity creates TAMs. By interacting with other microenvironment, promote progression. Here, we review origin, heterogeneity, functional roles In addition, discuss prospects therapeutically targeting alone or combination standard newly-emerging therapies.

Язык: Английский

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Glial and myeloid heterogeneity in the brain tumour microenvironment

Nature reviews. Cancer, Год журнала: 2021, Номер 21(12), С. 786 - 802

Опубликована: Сен. 28, 2021

Язык: Английский

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Mechanisms and Models of Kidney Tubular Necrosis and Nephron Loss

Journal of the American Society of Nephrology, Год журнала: 2022, Номер 33(3), С. 472 - 486

Опубликована: Янв. 12, 2022

Understanding nephron loss is a primary strategy for preventing CKD progression. Death of renal tubular cells may occur by apoptosis during developmental and regenerative processes. However, AKI, the transition AKI to CKD, sepsis-associated kidney transplantation ferroptosis necroptosis, two pathways associated with plasma membrane integrity, kill cells. This necrotic type cell death an inflammatory response, which referred as necroinflammation. Importantly, necroinflammatory response that die necroptosis be fundamentally different from tissue ferroptosis. Although mechanisms have recently been investigated in detail, propagation necrosis, although described morphologically, remains incompletely understood. Here, we argue molecular switch downstream necrosis determines regeneration versus loss. Unraveling details this "switch" must include signals potentially controlled cells, including stimulation myofibroblasts origin fibrosis. detail responses can inform discussion therapeutic options.

Язык: Английский

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