Complex interplay between autophagy and oxidative stress in the development of pulmonary disease

Redox Biology, Journal Year: 2020, Volume and Issue: 36, P. 101679 - 101679

Published: Aug. 11, 2020

The autophagic pathway involves the encapsulation of substrates in double-membraned vesicles, which are subsequently delivered to lysosome for enzymatic degradation and recycling metabolic precursors. Autophagy is a major cellular defense against oxidative stress, or related conditions that cause accumulation damaged proteins organelles. Selective forms autophagy can maintain organelle populations remove aggregated proteins. Dysregulation redox homeostasis under pathological results excessive generation reactive oxygen species (ROS), leading stress associated damage components. Accumulating evidence indicates necessary homeostasis. ROS activates autophagy, facilitates adaptation diminishes by degrading intracellular macromolecules dysfunctional responses triggered include altered regulation signaling pathways culminate autophagy. Current research suggests central role as mammalian response its interrelationship other systems. Altered phenotypes have been observed lung diseases such chronic obstructive disease, acute injury, cystic fibrosis, idiopathic pulmonary arterial hypertension, asthma. Understanding mechanisms regulate will provide novel therapeutic targets diseases. This review highlights our current understanding on interplay between development disease.

Language: Английский

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Defective mitophagy in Alzheimer’s disease

Ageing Research Reviews, Journal Year: 2020, Volume and Issue: 64, P. 101191 - 101191

Published: Oct. 3, 2020

Language: Английский

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Targeting autophagy in disease: established and new strategies

Autophagy, Journal Year: 2021, Volume and Issue: 18(3), P. 473 - 495

Published: July 9, 2021

Macroautophagy/autophagy is an evolutionarily conserved pathway responsible for clearing cytosolic aggregated proteins, damaged organelles or invading microorganisms. Dysfunctional autophagy leads to pathological accumulation of the cargo, which has been linked a range human diseases, including neurodegenerative infectious and autoimmune diseases various forms cancer. Cumulative work in animal models, application genetic tools pharmacologically active compounds, suggested potential therapeutic value modulation disease, as diverse Huntington, Salmonella infection, pancreatic Autophagy activation versus inhibition strategies are being explored, while role pathophysiology studied parallel. However, progress preclinical clinical development modulators greatly hampered by paucity selective pharmacological agents biomarkers dissect their precise impact on cellular responses. Here, we summarize established new autophagy-related drug discovery indicate path toward establishing more efficient autophagy-selective agents. With this knowledge at hand, modern concepts exploitation might become plausible.Abbreviations: ALS: amyotrophic lateral sclerosis; AMPK: AMP-activated protein kinase; ATG: gene; AUTAC: autophagy-targeting chimera; CNS: central nervous system; CQ: chloroquine; GABARAP: gamma-aminobutyric acid type A receptor-associated protein; HCQ: hydroxychloroquine; LYTAC: lysosome targeting MAP1LC3/LC3: microtubule associated 1 light chain 3; MTOR: mechanistic target rapamycin NDD: disease; PDAC: ductal adenocarcinoma; PE: phosphatidylethanolamine; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit PtdIns3K: class III 3-kinase; PtdIns3P: 3-phosphate; PROTAC: proteolysis-targeting SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; SQSTM1/p62: sequestosome 1; ULK1: unc-51 like activating kinase 1.

Language: Английский

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The Role of Oxidative Stress in the Pathogenesis of Vitiligo: A Culprit for Melanocyte Death

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 12

Published: Jan. 22, 2022

Vitiligo is a common chronic acquired pigmentation disorder characterized by loss of pigmentation. Among various hypotheses proposed for the pathogenesis vitiligo, oxidative stress-induced immune response that ultimately leads to melanocyte death remains most widely accepted. Oxidative stress which causes elevated levels reactive oxygen species (ROS) can lead dysfunction molecules and organelles, triggering further response, death. In recent years, variety cell modes have been studied, including apoptosis, autophagy autophagic death, ferroptosis, other novel will be discussed in this review detail. also strongly linked these Under stress, ROS could induce activating Nrf2 antioxidant pathway melanocytes. However, persistent stimulation might eventually excessive activation pathway, turn inactivate autophagy. Moreover, ferroptosis may triggered oxidative-related transcriptional production, ARE, positive feedback loop related p62, reduced activity expression GPX4. Therefore, it reasonable infer are involved acts as an initiator through some complex mechanisms. study, we aim summarize role vitiligo discuss corresponding mechanisms interaction between stress. These findings provide new ideas exploring potential therapeutic targets vitiligo.

Language: Английский

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Premature ovarian insufficiency: a review on the role of oxidative stress and the application of antioxidants

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 1, 2023

Normal levels of reactive oxygen species (ROS) play an important role in regulating follicular growth, angiogenesis and sex hormone synthesis ovarian tissue. When the balance between ROS antioxidants is disrupted, however, it can cause serious consequences oxidative stress (OS), quantity quality oocytes will decline. Therefore, this review discusses interrelationship OS premature insufficiency (POI), potential mechanisms methods by which improve POI through controlling level OS. We found that mediate changes genetic materials, signal pathways, transcription factors microenvironment, resulting abnormal apoptosis granulosa cells (GCs) meiosis as well decreased mitochondrial Deoxyribonucleic Acid(mtDNA) other changes, thus accelerating process aging. However, antioxidants, mesenchymal stem (MSCs), biological enzymes delay disease reducing vivo .

Language: Английский

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The Role of Autophagy in Osteoarthritis

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

Published: Nov. 25, 2020

Chondrocytes are the only cell type in normal cartilage. The pathological changes of osteoarthritis (OA) mostly revolve around apoptosis and dysfunction chondrocytes. Autophagy, as an intracellular degradation system that maintains steady state energy metabolism cells, has been shown to restore function damaged chondrocytes, alleviating occurrence progression OA. In this review, we explored relationship between autophagy OA key molecules pathway regulate OA, providing new ideas for treatment by targeting autophagy.

Language: Английский

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Crosstalks between inflammasome and autophagy in cancer

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

Published: July 23, 2020

Abstract Both inflammasomes and autophagy have important roles in the intracellular homeostasis, inflammation, pathology; dysregulation of these processes is often associated with pathogenesis numerous cancers. In addition, they can crosstalk each other multifaceted ways to influence various physiological pathological responses, including cancer. Multiple molecular mechanisms connect pathway inflammasome activation and, through this, may outcome pro-tumor or anti-tumor responses depending on cancer types, microenvironment, disease stage. this review, we highlight rapidly growing literature by which interacts pathway, encourage additional applications context tumors. provide insight into pathogen modulates autophagy-inflammasome favor infection-induced carcinogenesis. We also explore challenges opportunities using multiple small molecules/agents target autophagy/inflammasome axis their effects upon treatment. Finally, discuss emerging clinical efforts assessing potential usefulness targeting approaches for either as anti-cancer strategies, although it remains underexplored terms crosstalks.

Language: Английский

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Interactions between reactive oxygen species and autophagy

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2021, Volume and Issue: 1868(8), P. 119041 - 119041

Published: April 17, 2021

Language: Английский

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Mitochondrial Reactive Oxygen Species: Double-Edged Weapon in Host Defense and Pathological Inflammation During Infection

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 14, 2020

Mitochondria are inevitable sources for the generation of mitochondrial reactive oxygen species (mtROS) due to their fundamental roles in respiration. mtROS were reported be bactericidal weapons with an innate effector function during infection. However, controlled is vital induction efficient immune responses because excessive production damage leads sustained inflammation, resulting pathological outcomes such as sepsis. Here, we discuss beneficial and detrimental system bacterial, viral, fungal infections. Recent evidence suggests that several pathogens have evolved multiple strategies modulate own benefit. We just beginning understand mechanisms by which regulated how affect protective Several agents/small molecules prevent uncontrolled known maintenance tissue homeostasis mtROS-targeted approaches need incorporated into preventive therapeutic against a variety

Language: Английский

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The Role of Cholesterol in α‐Synuclein and Lewy Body Pathology in GBA1 Parkinson's Disease

Movement Disorders, Journal Year: 2020, Volume and Issue: 36(5), P. 1070 - 1085

Published: Nov. 21, 2020

ABSTRACT Parkinson's disease (PD) is a progressive neurodegenerative where dopaminergic neurons in the substantia nigra are lost, resulting decrease striatal dopamine and, consequently, motor control. Dopaminergic degeneration associated with appearance of Lewy bodies, which contain membrane structures and proteins, including α‐synuclein (α‐Syn), surviving neurons. PD displays multifactorial pathology develops from interactions between multiple elements, such as age, environmental conditions, genetics. Mutations GBA1 gene represent one major genetic risk factors for PD. This encodes an essential lysosomal enzyme called β‐glucocerebrosidase (GCase), responsible degrading glycolipid glucocerebroside into glucose ceramide. GCase can generate glucosylated cholesterol via transglucosylation also degrade sterol glucoside. Although molecular mechanisms that predispose individual to neurodegeneration remain unknown, role deserves consideration. Disturbed cellular metabolism, reflected by accumulation ‐associated models, could contribute changes lipid rafts, necessary synaptic localization vesicle cycling modulation integrity. α‐Syn has been implicated regulation neuronal cholesterol, facilitates oligomers. In this review, we integrate results previous studies describe landscape homeostasis function. We discuss its implication body pathophysiological underlying PD, focusing on cholesterol. © 2020 The Authors. Movement Disorders published Wiley Periodicals LLC behalf International Parkinson Disorder Society

Language: Английский

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