Targeting pyroptosis as a preventive and therapeutic approach for stroke DOI Creative Commons
Junpeng Long, Yang Sun, Shasha Liu

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: May 10, 2023

Stroke has caused tremendous social stress worldwide, yet despite decades of research and development new stroke drugs, most have failed rt-PA (Recombinant tissue plasminogen activator) is still the accepted treatment for ischemic stroke. complexity mechanism led to unsatisfactory efficacy drugs in clinical trials, indicating that there are many gaps our understanding Pyroptosis a programmed cell death (PCD) with inflammatory properties thought be closely associated regulated by GSDMD gasdermin family, which when cleaved Caspase-1/Caspase-11 into N-GSDMD pore-forming activity can bind plasma membrane form small 10-20 nm pores, would allow release factors IL-18 IL-1β before rupture, greatly exacerbating response. The pyroptosis occurs mainly border zone cerebral infarction, glial cells, neuronal cells brain microvascular endothelial (BMECs) all undergo after stroke, largely exacerbates breakdown blood-brain barrier (BBB) thus aggravates injury. Therefore, may good direction In this review, we focus on latest mechanisms action process regulates development. We also suggest potential therapeutic target pathway, providing additional strategies management role After microglia first rush damaged area polarize M1 M2 types. Under influence various stimuli, pyroptosis, pro-inflammatory factors, converted type; astrocytes under stimulation leading astrocyte due increased osmotic pressure membrane, resulting water absorption swelling until rupture. BMECs, main structural component BBB, stimulated released from astrocytes, destruction integrity ultimately causing more severe damage. addition, neutrophils mediate NETs rather than IL-10=interleukin-10; TGF-β = transforming growth factor-β; IL-18=interleukin-18; interleukin-1β; TNF-α tumor necrosis factor-α; iNOS=induced nitrogen monoxide synthase; MMPs=Matrix metalloproteinases; D; BMECs=brain cells; BBB barrier.

Language: Английский

Immunogenic cell stress and death DOI Open Access
Guido Kroemer,

Claudia Galassi,

Laurence Zitvogel

et al.

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(4), P. 487 - 500

Published: Feb. 10, 2022

Language: Английский

Citations

844
Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics DOI Creative Commons

Uttpal Anand,

Abhijit Dey, Arvind K. Singh Chandel

et al.

Genes & Diseases, Journal Year: 2022, Volume and Issue: 10(4), P. 1367 - 1401

Published: March 18, 2022

Cancer is an abnormal state of cells where they undergo uncontrolled proliferation and produce aggressive malignancies that causes millions deaths every year. With the new understanding molecular mechanism(s) disease progression, our knowledge about snowballing, leading to evolution many therapeutic regimes their successive trials. In past few decades, various combinations therapies have been proposed are presently employed in treatment diverse cancers. Targeted drug therapy, immunotherapy, personalized medicines now largely being employed, which were not common a years back. The field cancer discoveries therapeutics evolving fast as type-specific biomarkers progressively identified several types cancers nowadays undergoing systematic therapies, extending patients' disease-free survival thereafter. Although growing evidence shows targeted approach could be future medicine, chemotherapy remains opted option despite its known side effects on patient's physical psychological health. Chemotherapeutic agents/pharmaceuticals served great purpose over decades remained frontline choice for advanced-stage surgery and/or radiation therapy cannot prescribed due specific reasons. present report succinctly reviews existing contemporary advancements assesses status enrolled drugs/pharmaceuticals; it also comprehensively discusses emerging role specific/targeted strategies achieve better clinical success/survival rate patients.

Language: Английский

Citations

755
Ferroptosis at the intersection of lipid metabolism and cellular signaling DOI Creative Commons
Deguang Liang, Alexander M. Minikes, Xuejun Jiang

et al.

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(12), P. 2215 - 2227

Published: April 6, 2022

Language: Английский

Citations

628
Molecular mechanisms of cell death in neurological diseases DOI Creative Commons
Diane Moujalled, Andreas Strasser, Jeffrey R. Liddell

et al.

Cell Death and Differentiation, Journal Year: 2021, Volume and Issue: 28(7), P. 2029 - 2044

Published: June 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.

Language: Английский

Citations

492
Current understanding of osteoarthritis pathogenesis and relevant new approaches DOI Creative Commons
Liping Tong, Huan Yu, Xingyun Huang

et al.

Bone Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: Sept. 20, 2022

Abstract Osteoarthritis (OA) is the most common degenerative joint disease that causes painful swelling and permanent damage to joints in body. The molecular mechanisms of OA are currently unknown. a heterogeneous affects entire joint, multiple tissues altered during development. To better understand pathological OA, new approaches, methods, techniques need be used pathogenesis. In this review, we first focus on epigenetic regulation with particular DNA methylation, histone modification, microRNA regulation, followed by summary several key mediators OA-associated pain. We then introduce innovative have been will continue fields pain, such as CRISPR, scRNA sequencing, lineage tracing. Next, discuss timely updates concerning cell death pathology, including pyroptosis, ferroptosis, autophagy, well their individual roles potential targets treating OA. Finally, our review highlights directions role synovial lymphatic system An improved understanding pathogenesis aid development more specific effective therapeutic interventions for

Language: Английский

Citations

217
Apoptotic cell death in disease—Current understanding of the NCCD 2023 DOI Open Access
Ilio Vitale, Federico Pietrocola, Emma Guilbaud

et al.

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(5), P. 1097 - 1154

Published: April 26, 2023

Language: Английский

Citations

211
Cytosolic escape of mitochondrial DNA triggers cGAS-STING-NLRP3 axis-dependent nucleus pulposus cell pyroptosis DOI Creative Commons
Weifeng Zhang, Gaocai Li,

Rongjin Luo

et al.

Experimental & Molecular Medicine, Journal Year: 2022, Volume and Issue: 54(2), P. 129 - 142

Published: Feb. 1, 2022

Abstract Low back pain (LBP) is a major musculoskeletal disorder and the socioeconomic problem with high prevalence that mainly involves intervertebral disc (IVD) degeneration, characterized by progressive nucleus pulposus (NP) cell death development of an inflammatory microenvironment in NP tissue. Excessively accumulated cytosolic DNA acts as damage-associated molecular pattern (DAMP) monitored cGAS-STING axis to trigger immune response many degenerative diseases. NLRP3 inflammasome-dependent pyroptosis type programmed promotes chronic tissue degeneration. However, relationship between inflammasome-induced pathogenesis IVD degeneration remains unclear. Here, we used magnetic resonance imaging (MRI) histopathology demonstrate cGAS, STING, are associated degree Oxidative stress induced activation inflammasome-mediated STING-dependent manner human cells. Interestingly, canonical morphological functional characteristics mitochondrial permeability transition pore (mPTP) opening escape (mtDNA) were observed cells under oxidative stress. Furthermore, administration specific pharmacological inhibitor mPTP self-mtDNA leakage effectively reduced pyroptotic microenvironmental inflammation vitro progression rat needle puncture model. Collectively, these data highlight critical roles cGAS-STING-NLRP3 provide promising therapeutic approaches for discogenic LBP.

Language: Английский

Citations

194
Insights into N6-methyladenosine and programmed cell death in cancer DOI Creative Commons
Li Liu, Hui Li, Dingyu Hu

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 28, 2022

Abstract N6-methyladenosine (m6A) methylation, the most common form of internal RNA modification in eukaryotes, has gained increasing attention and become a hot research topic recent years. M6A plays multifunctional roles normal abnormal biological processes, its role may vary greatly depending on position m6A motif. Programmed cell death (PCD) includes apoptosis, autophagy, pyroptosis, necroptosis ferroptosis, which involve breakdown plasma membrane. Based implications methylation PCD, regulators functional were comprehensively studied reported. In this review, we focus high-complexity links between different types PCD pathways, are then closely associated with initiation, progression resistance cancer. Herein, clarifying relationship is great significance to provide novel strategies for cancer treatment, potential prospect clinical application.

Language: Английский

Citations

176
The Pyroptosis-Related Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Gastric Cancer DOI Creative Commons
Wei Shao, Zongcheng Yang, Yue Fu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: June 11, 2021

Gastric cancer (GC) is one of the leading causes cancer-related deaths and shows high levels heterogeneity. The development a specific prognostic model important if we are to improve treatment strategies. Pyroptosis can arise in response H. pylori , primary carcinogen, also chemotherapy drugs. However, evaluation GC pyroptosis insufficient. Consensus clustering by pyroptosis-related regulators was used classify 618 patients with from four GEO cohorts. Following Cox regression differentially expressed genes, our prognosis (PS-score) built LASSO-Cox analysis. TCGA-STAD cohort as validation set. ESTIMATE, CIBERSORTx, EPIC were investigate tumor microenvironment (TME). Immunotherapy cohorts blocking PD1 / PD-L1 response. subtyping based on able according different clinical traits TME. difference between two subtypes identified this study develop which named “PS-score.” PS-score could predict his/her overall survival time. A low implies greater inflammatory cell infiltration better immunotherapy blockers. Our findings provide foundation for future research targeting its immune responses immunotherapy.

Language: Английский

Citations

159
Regulated cell death pathways in kidney disease DOI Open Access
Ana B. Sanz, María Dolores Sánchez-Niño, Adrián M. Ramos

et al.

Nature Reviews Nephrology, Journal Year: 2023, Volume and Issue: 19(5), P. 281 - 299

Published: March 23, 2023

Language: Английский

Citations

158