Implications of endoplasmic reticulum stress and autophagy in aging and cardiovascular diseases

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Июль 25, 2024

The average lifespan of humans has been increasing, resulting in a rapidly rising percentage older individuals and high morbidity aging-associated diseases, especially cardiovascular diseases (CVDs). Diverse intracellular extracellular factors that interrupt homeostatic functions the endoplasmic reticulum (ER) induce ER stress. Cells employ dynamic signaling pathway unfolded protein response (UPR) to buffer Recent studies have demonstrated stress triggers various cellular processes associated with aging many including CVDs. Autophagy is conserved process involving lysosomal degradation recycling cytoplasmic components, proteins, organelles, pathogens invade cytoplasm. vital for combating adverse influence on heart. present report summarizes recent mechanism autophagy their overlap CVD pathogenesis context aging. It also discusses possible therapeutic interventions targeting might delay prevent or treat

Язык: Английский

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Orf132: A Critical Gene for LSDV Replication and Its Role in ER Stress-Related Apoptosis

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Lumpy skin disease (LSD), caused by lumpy virus (LSDV), is an emerging infectious in China that primarily affects cattle. LSDV and goatpox (GTPV) belong to the Capripoxvirus genus exhibit high genomic homology, enabling cross-immunogenicity. Comparative genome analysis revealed contains a unique gene, Orf132, whose function remains uncharacterized. In this study, we first confirmed recombinant ORF132 protein exhibits immunoreactivity against sera from LSDV-infected cattle GTPV-vaccinated cattle, cross-reactivity excluded possibility of using distinguish between GTPV. To investigate biological role generated Orf132 deletion strain (LSDV-ΔOrf132). Compared with wild-type LSDV, replication capacity LSDV-ΔOrf132 was reduced approximately tenfold, indicating critical for viral replication. Transcriptomic infected MDBK cells significant alterations Endoplasmic reticulum(ER) processing unfolded response(UPR) pathways following deletion. RT-qPCR validation showed marked upregulation ER stress markers including Grp78, Chop, Gadd34. Subsequent apoptosis assays established triggers CHOP-Caspase12-mediated apoptotic pathways. This dysregulated response cascade culminates premature scenarios, possibly resulting weakening Our findings collectively gene replication, plays essential virus's life cycle, its significantly impairs while inducing stress-related apoptosis.

Язык: Английский

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Melatonin regulation of phase separation in Neuro-PASC: out-maneuvering Janus-faced amyloids

Exploration of neuroscience, Год журнала: 2025, Номер 4

Опубликована: Март 24, 2025

The SAR-CoV-2 virus has evolved to co-exist with human hosts, albeit at a substantial energetic cost resulting in post-infection neurological manifestations [Neuro-post-acute sequelae of SARS-CoV-2 infection (PASC)] that significantly impact public health and economic productivity on global scale. One the main molecular mechanisms responsible for development Neuro-PASC, individuals all ages, is formation inadequate proteolysis/clearance phase-separated amyloid crystalline aggregates—a hallmark feature aging-related neurodegenerative disorders. Amyloidogenesis during viral persistence natural, inevitable, protective defense response exacerbated by SARS-CoV-2. Acting as chemical catalyst, accelerates hydrophobic collapse heterogeneous nucleation amorphous amyloids into stable β-sheet aggregates. clearance aggregates most effective slow wave sleep, when high levels adenosine triphosphate (ATP)—a biphasic modulator biomolecular condensates—and melatonin are available solubilize removal. dysregulation mitochondrial dynamics SARS-CoV-2, particular fusion fission homeostasis, impairs proper distinct subpopulations can remedy challenges created diversion substrates away from oxidative phosphorylation towards glycolysis support replication maintenance. subsequent reduction ATP inhibition synthesis sleep results incomplete brain aggregates, leading commonly associated age-related Exogenous not only prevents dysfunction but also elevates production, effectively augmenting solubilizing effect moiety ensure timely, optimal disaggregation pathogenic prevention attenuation Neuro-PASC.

Язык: Английский

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USP3 promotes clear cell renal cell carcinoma progression by stabilizing MYC and enhancing glycolysis

Biochimica et Biophysica Acta (BBA) - General Subjects, Год журнала: 2025, Номер unknown, С. 130801 - 130801

Опубликована: Март 1, 2025

Язык: Английский

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Neurotropic Viruses as Acute and Insidious Drivers of Aging

Biomolecules, Год журнала: 2025, Номер 15(4), С. 514 - 514

Опубликована: Апрель 1, 2025

Aging is the result of various compounding stresses that gradually overcome homeostatic regulation cell, resulting in irreversible damage. This manifests as many acute and chronic conditions, most common which are neurodegeneration dementia. Epidemiological studies have shown significant, strong correlations between viral infection neurodegenerative diseases. review overlays characteristics pathogenesis with hallmarks aging to discuss how active latent viruses contribute aging. Through our contextualization myriad basic science papers, we offer explanations for premature via induction stress response pathways. Viruses induce stresses: dysregulated homeostasis by exogenous proteins overwhelmed protein quality control mechanisms, DNA damage through direct integration epigenetic manipulation, immune-mediated oxidative immune exhaustion, general energy theft amplified an system. Overall, this highlights long-term importance vaccines antivirals addition their benefits.

Язык: Английский

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Stable expression of SARS-CoV-2 envelope viroporin promotes intracellular calcium depletion in human cells: relevance for endoplasmic reticulum stress, cell proliferation, pluripotency and lineage differentiation

Cell Calcium, Год журнала: 2025, Номер 128, С. 103032 - 103032

Опубликована: Апрель 18, 2025

Язык: Английский

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Orf132: a critical gene for LSDV replication and its role in Er stress-related apoptosis

Virology Journal, Год журнала: 2025, Номер 22(1)

Опубликована: Май 30, 2025

Язык: Английский

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Effect of Melatonin on Herpesvirus Type 1 Replication

Опубликована: Фев. 29, 2024

Acute HSV-1 infection is associated with mild symptom, such as fever and lesions of the mouth, face skin. This phase followed by a latency period before reactivation which symptoms ranging from ulcers to encephalitis. Despite available anti-HSV-1 drugs, development new antiviral agents sought due presence resistant viruses. Melatonin, molecule secreted pineal gland, has been shown be an antioxidant, inducer antioxidant enzymes, regulator various biological processes. Clinical trials have explored its therapeutic utility in conditions including infections. study focuses on melatonin's role replication underlying mechanisms. Melatonin was found decrease synthesis proteins infected Vero cells measured inmunofluorescence indicating inhibition replication. Additionally, it regulates activities enzymes affects proteasome activity. activates unfolded protein response (UPR) autophagy suppresses apoptosis HSV-1-infected cells. In summary, melatonin demonstrates inhibitory modulating cellular responses, suggesting potential treatment viral

Язык: Английский

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Effect of Melatonin on Herpesvirus Type 1 Replication

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 4037 - 4037

Опубликована: Апрель 4, 2024

Acute HSV-1 infection is associated with mild symptoms, such as fever and lesions of the mouth, face skin. This phase followed by a latency period before reactivation, which symptoms ranging from ulcers to encephalitis. Despite available anti-HSV-1 drugs, development new antiviral agents sought due presence resistant viruses. Melatonin, molecule secreted pineal gland, has been shown be an antioxidant, inducer antioxidant enzymes, regulator various biological processes. Clinical trials have explored its therapeutic utility in conditions including infections. study focuses on melatonin’s role replication underlying mechanisms. Melatonin was found decrease synthesis proteins infected Vero cells measured immunofluorescence, indicating inhibition replication. Additionally, it regulates activities enzymes affects proteasome activity. activates unfolded protein response (UPR) autophagy suppresses apoptosis HSV-1-infected cells. In summary, melatonin demonstrates inhibitory modulating cellular responses, suggesting potential treatment viral

Язык: Английский

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Exploring Bioactive Compounds of Rauvolfia tetraphylla L. (RT) for 3CLprotease of SARS-CoV2: GC-MS Analysis and In-Silico Studies

Cell Biochemistry and Biophysics, Год журнала: 2024, Номер 82(4), С. 3383 - 3393

Опубликована: Июль 20, 2024

Язык: Английский

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