Mitophagy in degenerative joint diseases

Autophagy, Journal Year: 2020, Volume and Issue: 17(9), P. 2082 - 2092

Published: Sept. 24, 2020

Mitochondrial dysfunction is involved in aging and multiple degenerative diseases, including intervertebral disc degeneration (IVDD) osteoarthritis (OA). Thus, the maintenance of mitochondria homeostasis function important. Mitophagy, a process that selectively clears damaged or dysfunctional through autophagic machinery, functions to maintain mitochondrial quality control homeostasis. IVDD OA are similar joint diseases involving degradation cartilaginous tissues mainly caused by oxidative stress, cell apoptosis extracellular matrix (ECM) degradation. Over past decade, accumulating evidence indicates essential role mitophagy pathogenesis OA. Importantly, strategies regulation exert beneficial effects pre-clinical experiments. Given importance novelty mitophagy, we provide an overview pathways discuss roles We also highlight potential targeting for treatment diseases.Abbreviations: AD: Alzheimer disease; AF: annulus fibrosus; ADORA2A/A2AR: adenosine A2a receptor; AMBRA1: autophagy beclin 1 regulator 1; BMSCs: bone marrow mesenchymal stem cells; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B 3-like; CDH6: cadherin 6; CEP: endplates; circRNA: circular RNA; DNM1L/DRP1: dynamin 1-like; ECM: matrix; HIF1A: hypoxia inducible factor 1: alpha subunit; IL1B: interleukin beta; IMM: inner membranes; IVDD: degeneration; MAPK8/JNK: mitogen-activated kinase 8; MFN1: mitofusin MFN2: 2; MIA: monosodium iodoacetate; RHOT/MIRO: ras homolog family member T; MMP: transmembrane potential; CALCOCO2/NDP52: calcium binding coiled-coil domain NFE2L2: nuclear factor: erythroid 2 like NP: nucleus pulposus; OA: osteoarthritis; OPA1: GTPase; OPTN: optineurin; PRKN: parkin RBR E3 ubiquitin ligase; PD: Parkinson PGAM5: PGAM 5; PPARGC1A/PGC-1A: peroxisome proliferator activated receptor: gamma: coactivator alpha; PHF23: PHD finger 23; PINK1: PTEN induced putative ROS: reactive oxygen species; SfMSCs: synovial fluid MSCs; SIRT1: sirtuin SIRT2: SIRT3: SQSTM1/p62: sequestosome TNF: tumor necrosis factor; Ub: ubiquitin; UBL: ubiquitin-like; VDAC: voltage-dependent anion channel.

Language: Английский

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Molecular Bases of VEGFR-2-Mediated Physiological Function and Pathological Role

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Nov. 16, 2020

The VEGF/VEGFR-2 system participates in vasculogenesi and angiogenesis. Angiogenesis, as an important mechanism many physiological pathological processes, is involved endothelial cell proliferation, migration, survival, leads to further tubulogenesis, finally promotes formation of vessels. This series signaling cascade pathways are precisely mediated by system. VEGF binding the IgD2 IgD3 VEGFR-2 induces dimerization receptor, subsequently activation trans-autophosphorylation tyrosine kinase, then initiation intracellular cascades, VEGF-activated stimulates mediates variety transduction, biological responses, processes angiogenesis, which several crucial phosphorylated sites Tyr801, Try951, Try1175, Try1214 domains mediate key including PLCγ-PKC, TSAd-Src-PI3K-Akt, SHB-FAK-paxillin, SHB-PI3K-Akt, NCK-p38-MAPKAPK2/3 pathways. Based on molecular structure VEGFR-2, strategy VEGFR-2-targeted therapy should be considered employ treatment this system-associated diseases blocking pathway, inhibiting gene expression, destroying vascular cells expressing VEGFR-2.

Language: Английский

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Copper metabolism in cell death and autophagy

Autophagy, Journal Year: 2023, Volume and Issue: 19(8), P. 2175 - 2195

Published: April 14, 2023

Copper is an essential trace element in biological systems, maintaining the activity of enzymes and function transcription factors. However, at high concentrations, copper ions show increased toxicity by inducing regulated cell death, such as apoptosis, paraptosis, pyroptosis, ferroptosis, cuproptosis. Furthermore, can trigger macroautophagy/autophagy, a lysosome-dependent degradation pathway that plays dual role regulating survival or death fate cells under various stress conditions. Pathologically, impaired metabolism due to environmental genetic causes implicated variety human diseases, rare Wilson disease common cancers. Therapeutically, copper-based compounds are potential chemotherapeutic agents be used alone combination with other drugs approaches treat cancer. Here, we review progress made understanding metabolic processes their impact on regulation autophagy. This knowledge may help design future clinical tools improve cancer diagnosis treatment.

Language: Английский

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Autophagy in tumour immunity and therapy

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(5), P. 281 - 297

Published: March 23, 2021

Language: Английский

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Long non-coding RNAs towards precision medicine in gastric cancer: early diagnosis, treatment, and drug resistance

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: May 27, 2020

Gastric cancer is a deadly disease and remains the third leading cause of cancer-related death worldwide. The 5-year overall survival rate patients with early-stage localized gastric more than 60%, whereas that distant metastasis less 5%. Surgical resection best option for cancer, while chemotherapy mainly used in middle advanced stages this disease, despite frequently reported treatment failure due to resistance. Therefore, there an unmet medical need identifying new biomarkers early diagnosis proper management patients, achieve response treatment. Long non-coding RNAs (lncRNAs) body fluids have attracted widespread attention as screening, diagnosis, treatment, prognosis, responses drugs high specificity sensitivity. In present review, we focus on clinical potential lncRNAs liquid biopsies prognosis cancer. We also comprehensively discuss roles their molecular mechanisms chemoresistance well therapeutic targets precision medicine.

Language: Английский

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Liquid–liquid phase separation drives cellular function and dysfunction in cancer

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(4), P. 239 - 252

Published: Feb. 11, 2022

Language: Английский

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Various Aspects of Calcium Signaling in the Regulation of Apoptosis, Autophagy, Cell Proliferation, and Cancer

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(21), P. 8323 - 8323

Published: Nov. 6, 2020

Calcium (Ca2+) is a major second messenger in cells and essential for the fate survival of all higher organisms. Different Ca2+ channels, pumps, or exchangers regulate variations duration levels intracellular Ca2+, which may be transient sustained. These changes are then decoded by an elaborate toolkit Ca2+-sensors, translate signal to operational cell machinery, thereby regulating numerous Ca2+-dependent physiological processes. Alterations homoeostasis signaling often deleterious associated with certain pathological states, including cancer. Altered transmission has been implicated variety processes fundamental uncontrolled proliferation invasiveness tumor other important cancer progression, such as development resistance therapies. Here, we review what known about how this regulates life death decisions context cancer, particular attention directed proliferation, apoptosis, autophagy. We also explore intersections therapeutic targeting cells, summarizing opportunities modulators improve effectiveness current anticancer

Language: Английский

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Targeting autophagy to overcome drug resistance: further developments

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Nov. 25, 2020

Abstract Inhibiting cell survival and inducing death are the main approaches of tumor therapy. Autophagy plays an important role on intracellular metabolic homeostasis by eliminating dysfunctional or unnecessary proteins damaged aged cellular organelles to recycle their constituent metabolites that enable maintenance genetic stability even promotes drug resistance, which severely limits efficacy chemotherapeutic drugs. Currently, targeting autophagy has a seemingly contradictory effect suppress promote survival, makes resistance more confusing fuzzier. In review, we summarize regulation emerging ways, action some new therapeutic treat interfering with autophagy-related pathways. The full-scale understanding tumor-associated signaling pathways physiological functions will hopefully open possibilities for treatment improvement in clinical outcomes.

Language: Английский

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Ubiquitination-Proteasome System (UPS) and Autophagy Two Main Protein Degradation Machineries in Response to Cell Stress

Cells, Journal Year: 2022, Volume and Issue: 11(5), P. 851 - 851

Published: March 1, 2022

In response to environmental stimuli, cells make a series of adaptive changes combat the injury, repair damage, and increase tolerance stress. However, once damage is too serious repair, will undergo apoptosis protect overall through suicidal behavior. Upon external stimulation, some intracellular proteins turn into unfolded or misfolded protein, exposing their hydrophobic regions form protein aggregation, which may ultimately produce cells. Ubiquitin plays an important role in degradation these unnatural by tagging with ubiquitin chains ubiquitin-proteasome autophagy system. If two processes fail eliminate abnormal aggregates, move death. Dysregulation system (UPS) result development numerous diseases. This review focuses on molecular mechanisms UPS clearance relationship between dysregulation network

Language: Английский

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Autophagy: A Key Regulator of Homeostasis and Disease: An Overview of Molecular Mechanisms and Modulators

Cells, Journal Year: 2022, Volume and Issue: 11(15), P. 2262 - 2262

Published: July 22, 2022

Autophagy is a highly conserved lysosomal degradation pathway active at basal levels in all cells. However, under stress conditions, such as lack of nutrients or trophic factors, it works survival mechanism that allows the generation metabolic precursors for proper functioning cells until are available. Neurons, post-mitotic cells, depend largely on autophagy to maintain cell homeostasis get rid damaged and/or old organelles and misfolded aggregated proteins. Therefore, dysfunction this process contributes pathologies many human diseases. Furthermore, during differentiation development. In review, we describe current knowledge different pathways, molecular mechanisms, factors induce it, regulation mammalian autophagy. We also discuss its relevant role development disease. Finally, here summarize several investigations demonstrating autophagic abnormalities have been considered underlying reasons diseases, including liver disease, cardiovascular, cerebrovascular neurodegenerative neoplastic cancers, and, more recently, infectious SARS-CoV-2 caused COVID-19

Language: Английский

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