Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells DOI Creative Commons
Suelen da Silva Gomes Dias, Tamires Cunha‐Fernandes, Luciana Souza‐Moreira

и другие.

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Март 8, 2023

Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disorders and congenital diseases in newborns. Host lipid metabolism, including droplet (LD) biogenesis, has been associated with viral replication pathogenesis of different viruses. However, the mechanisms LD formation their roles ZIKV neural cells are still unclear. Here, we demonstrate that regulates expression pathways upregulation activation lipogenesis-associated transcription factors decreased lipolysis-associated proteins, leading significant accumulation human neuroblastoma SH-SY5Y stem (NSCs). Pharmacological inhibition DGAT-1 vitro an vivo mouse model infection. In accordance role LDs regulation inflammation innate immunity, show blocking major inflammatory cytokine production brain. Moreover, observed inhibited weight loss mortality induced by vivo. Our results reveal biogenesis triggered crucial step for cells. Therefore, targeting metabolism may represent potential strategies anti-ZIKV treatment development.

Язык: Английский

Lipid droplet biogenesis and functions in health and disease DOI Open Access

Armella Zadoorian,

Ximing Du, Hongyuan Yang

и другие.

Nature Reviews Endocrinology, Год журнала: 2023, Номер 19(8), С. 443 - 459

Опубликована: Май 23, 2023

Язык: Английский

Процитировано

278
Monocytes and Macrophages in COVID-19 DOI Creative Commons
Rainer Knoll, Joachim L. Schultze, Jonas Schulte-Schrepping

и другие.

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Июль 21, 2021

COVID-19 is a contagious viral disease caused by SARS-CoV-2 that led to an ongoing pandemic with massive global health and socioeconomic consequences. The characterized primarily, but not exclusively, respiratory clinical manifestations ranging from mild common cold symptoms, including cough fever, severe distress multi-organ failure. Macrophages, heterogeneous group of yolk-sac derived, tissue-resident mononuclear phagocytes complex ontogeny present in all mammalian organs, play critical roles developmental, homeostatic host defense processes tissue-dependent plasticity. In case infection, they are responsible for early pathogen recognition, initiation resolution inflammation, as well repair tissue damage. Monocytes, bone-marrow derived blood-resident phagocytes, recruited under pathological conditions such infections the affected defend organism against invading pathogens aid efficient inflammation. Given their pivotal function potential danger posed dysregulated hyperinflammation, understanding monocyte macrophage phenotypes key tackling disease's mechanisms. Here, we outline current knowledge on monocytes macrophages homeostasis summarize concepts findings role COVID-19. While blood patients moderate inflammatory, interferon-stimulated gene (ISG)-driven phenotype, cellular dysfunction epitomized loss HLA-DR expression induction S100 alarmin dominant feature disease. Pulmonary infiltrating inflammatory hyperactivated state resulting detrimental loop pro-inflammatory cytokine release recruitment cytotoxic effector cells thereby exacerbating damage at site infection.

Язык: Английский

Процитировано

242
The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle DOI Open Access
Simona Ricciardi, Andrea Maria Guarino, Laura Giaquinto

и другие.

Nature, Год журнала: 2022, Номер 606(7915), С. 761 - 768

Опубликована: Май 12, 2022

Язык: Английский

Процитировано

151
Dissecting lipid metabolism alterations in SARS-CoV-2 DOI Open Access

Ilaria Casari,

Marcello Manfredi, Pat Metharom

и другие.

Progress in Lipid Research, Год журнала: 2021, Номер 82, С. 101092 - 101092

Опубликована: Фев. 9, 2021

Язык: Английский

Процитировано

108
Modulation of Macrophage Immunometabolism: A New Approach to Fight Infections DOI Creative Commons
Thierry Gauthier, Wanjun Chen

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Янв. 26, 2022

Macrophages are essential innate immune cells that contribute to host defense during infection. An important feature of macrophages is their ability respond extracellular cues and adopt different phenotypes functions in response these stimuli. The evidence accumulated the last decade has highlighted crucial role metabolic reprogramming macrophage activation infectious context. Thus, understanding manipulation immunometabolism infection could be interest develop therapeutic strategies. In this review, we focus on 5 major pathways including glycolysis, pentose phosphate pathway, fatty acid oxidation synthesis, tricarboxylic cycle amino metabolism discuss how they sustain regulate function parasitic, bacterial viral infections as well trained immunity. At end, assess whether some drugs those used clinic development can target for potential therapy with an emphasis SARS-CoV2

Язык: Английский

Процитировано

90
Oxidative stress-induced endothelial dysfunction and decreased vascular nitric oxide in COVID-19 patients DOI Creative Commons
Virginie Montiel, Irina Lobysheva, Ludovic Gérard

и другие.

EBioMedicine, Год журнала: 2022, Номер 77, С. 103893 - 103893

Опубликована: Фев. 23, 2022

BackgroundSARS-CoV-2 targets endothelial cells through the angiotensin-converting enzyme 2 receptor. The resulting injury induces widespread thrombosis and microangiopathy. Nevertheless, early specific markers of dysfunction vascular redox status in COVID-19 patients are currently missing.MethodsObservational study including ICU non-ICU adult admitted hospital for acute respiratory failure, compared with control subjects matched cardiovascular risk factors similar to patients, septic shock unrelated COVID-19.FindingsEarly SARS-CoV-2 infection was associated an imbalance between exacerbated oxidative stress (plasma peroxides levels vs. controls: 1456.0 ± 400.2 vs 436 272.1 mmol/L; P < 0.05) a reduced nitric oxide bioavailability proportional disease severity (5-α-nitrosyl-hemoglobin, HbNO 116.1 62.1 163.3 46.7 nmol/L; 0.05). correlated oxygenation parameters (PaO2/FiO2 ratio) (R2 = 0.13; Plasma angiotensin II, aldosterone, renin or serum level TREM-1 ruled out any hyper-activation renin-angiotensin-aldosterone system leucocyte burst contrary patients.InterpretationEndothelial ensuing decreased NO appears as likely pathogenic factor patients. A correlation is observed hospitalized These results highlight urgent need oriented research leading better understanding that occurs during SARS-CoV-2.FundingStated acknowledgments section.

Язык: Английский

Процитировано

75
ATG14 targets lipid droplets and acts as an autophagic receptor for syntaxin18-regulated lipid droplet turnover DOI Creative Commons
Zhen Yuan, Kun Cai, Jiajia Li

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 20, 2024

Язык: Английский

Процитировано

21
Lipid Metabolism Modulation during SARS-CoV-2 Infection: A Spotlight on Extracellular Vesicles and Therapeutic Prospects DOI Open Access

Heloísa D’Ávila,

Claudia Natércia Rocha Lima,

Pollianne Garbero Rampinelli

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(1), С. 640 - 640

Опубликована: Янв. 4, 2024

Extracellular vesicles (EVs) have a significant impact on the pathophysiological processes associated with various diseases such as tumors, inflammation, and infection. They exhibit molecular, biochemical, entry control characteristics similar to viral infections. Viruses, other hand, depend host metabolic machineries fulfill their biosynthetic requirements. Due potential advantages biocompatibility, biodegradation, efficient immune activation, EVs emerged therapeutic targets against SARS-CoV-2 Studies COVID-19 patients shown that they frequently dysregulated lipid profiles, which are an increased risk of severe repercussions. Lipid droplets (LDs) serve organelles roles in metabolism energy homeostasis well having wide range functions The down-modulation lipids, sphingolipid ceramide eicosanoids, or transcriptional factors involved lipogenesis seem inhibit multiplication, suggesting involvement virus replication pathogenesis highlighting for drug development. Hence, this review focuses role modulation mechanism system evasion during infection explores application delivering substances mitigate

Язык: Английский

Процитировано

20
The role of DGAT1 and DGAT2 in regulating tumor cell growth and their potential clinical implications DOI Creative Commons
Boer Deng, Wei­min Kong,

Xiaochang Shen

и другие.

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Март 18, 2024

Abstract Lipid metabolism is widely reprogrammed in tumor cells. droplet a common organelle existing most mammal cells, and its complex dynamic functions maintaining redox metabolic balance, regulating endoplasmic reticulum stress, modulating chemoresistance, providing essential biomolecules ATP have been well established The balance between lipid formation catabolism critical to energy while the process of affects various for growth. imbalance synthesis fatty acids cells leads alteration content Diacylglycerol acyltransferase 1 diacylglycerol 2, enzymes that catalyze final step triglyceride synthesis, participate droplets regulation cell proliferation, migration invasion, prognosis tumor. Several 2 inhibitors developed over past decade shown anti-tumor effects preclinical models improvement clinical trials. In this review, we highlight key features acid different paradigms activities on migration, tumor, with hope these scientific findings will potential implications.

Язык: Английский

Процитировано

19
Inhibitors of VPS34 and fatty-acid metabolism suppress SARS-CoV-2 replication DOI Creative Commons
Caroline G. Williams, Alexander S. Jureka, Jesus A. Silvas

и другие.

Cell Reports, Год журнала: 2021, Номер 36(5), С. 109479 - 109479

Опубликована: Июль 20, 2021

Coronaviruses rely on host membranes for entry, establishment of replication centers, and egress. Compounds targeting cellular membrane biology lipid biosynthetic pathways have previously shown promise as antivirals are actively being pursued treatments other conditions. Here, we test small molecule inhibitors that target the PI3 kinase VPS34 or fatty acid metabolism anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity. Our studies determine compounds potent SARS-CoV-2 inhibitors. Mechanistic with multiple steps up- downstream synthase (FASN) identify importance triacylglycerol production protein palmitoylation requirements efficient viral RNA synthesis infectious virus production. Further, FASN knockout results in significantly impaired can be rescued supplementation. Together, these clarify roles promising avenues development countermeasures against SARS-CoV-2.

Язык: Английский

Процитировано

98