Role of TrkB.T1 in Glial Inflammatory Response Elicited by MHV DOI Open Access

Noora Heiratifar

Published: Jan. 1, 2023

In the present thesis, we used a rodent analogous coronavirus, murine hepatitis virus (MHV), in culture to directly assess its impact on astrocytic and microglial cells. Given increasing importance of brain neurotrophic factor (BDNF)-TrkB signaling system glial functioning, also assessed whether unique TrkB.T1 truncated isoform (the only BDNF receptor astrocytes) would modulate reactivity MHV viral infection. Our results largely support notion that readily infects astrocytes caused degree toxicity these The addition microglia modulated magnitude this effect greatly increased pro-inflammatory cytokine release. Furthermore, deficiency appeared reduce astrocyte viability morphology. These data may have useful implications for better understanding nature responses coronaviral infection TrkB such responses.

Language: Английский

The Orf9b protein of SARS-CoV-2 modulates mitochondrial protein biogenesis DOI Creative Commons
Svenja Lenhard, Sarah Gerlich, Azkia Khan

et al.

The Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 222(10)

Published: Aug. 8, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) expresses high amounts of the protein Orf9b to target mitochondrial outer membrane Tom70. Tom70 serves as an import receptor for precursors and, independently this function, is critical cellular antiviral response. Previous studies suggested that interferes with Tom70-mediated signaling, but its implication biogenesis unknown. In study, we expressed in human HEK293 cells and observed Orf9b-mediated depletion proteins, particularly respiring cells. To exclude was caused by response, generated a yeast system which function could be recapitulated. Upon expression these cells, again specific decline subset proteins general reduction volume. Thus, SARS-CoV-2 virus able modulate proteome direct effect on Tom70-dependent import.

Language: Английский

Citations

24
Induction of the Inflammasome by the SARS‐CoV‐2 Accessory Protein ORF9b, Abrogated by Small‐Molecule ORF9b Homodimerization Inhibitors DOI
Erika Zodda, Mònica Pons, Natàlia DeMoya‐Valenzuela

et al.

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(2)

Published: Feb. 1, 2025

ABSTRACT Viral accessory proteins play critical roles in viral escape from host innate immune responses and inflammatory pathogenesis. Here we show that the SARS‐CoV‐2 protein, ORF9b, but not other (ORF3a, ORF3b, ORF6, ORF7, ORF8, ORF9c, ORF10), strongly activates inflammasome‐dependent caspase‐1 A549 lung carcinoma cells THP‐1 monocyte‐macrophage cells. Exposure to lipopolysaccharide (LPS) ATP additively enhanced activation of by suggesting ORF9b LPS follow parallel pathways inflammasome caspase‐1. Following rational silico approaches, have designed small molecules capable inhibiting homodimerization which experimentally inhibited ORF9b‐ORF9b homotypic interactions, caused mitochondrial eviction ORF9b‐induced cells, cytokine release restored type I interferon (IFN‐I) signaling suppressed both cell models. These are first‐in‐class compounds targeting a protein for viral‐induced exacerbated inflammation responses, with potential mitigating severe immunopathogenic damage induced highly pathogenic coronaviruses restoring antiviral curtailed infection.

Language: Английский

Citations

1
Type 2 Diabetes Mellitus and Neurodegenerative Disorders: The Mitochondrial Connection DOI Creative Commons

Isabella R Baduini,

Jose E Castro Vildosola,

Sheida Kavehmoghaddam

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: unknown, P. 107439 - 107439

Published: Sept. 1, 2024

Language: Английский

Citations

7
Plasma proteomics show altered inflammatory and mitochondrial proteins in patients with neurologic symptoms of post-acute sequelae of SARS-CoV-2 infection DOI

Barbara A. Hanson,

Lavanya Visvabharathy, Zachary S. Orban

et al.

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 114, P. 462 - 474

Published: Sept. 11, 2023

Language: Английский

Citations

15
Melatonin regulation of phase separation in Neuro-PASC: out-maneuvering Janus-faced amyloids DOI Creative Commons
Doris Loh, Russel J. Reıter

Exploration of neuroscience, Journal Year: 2025, Volume and Issue: 4

Published: March 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.

Language: Английский

Citations

0
COVID‐19 and neurodegeneration: The mitochondrial connection DOI Creative Commons

Christopher Anthony Denaro,

Yara I. Haloush,

Samuel Yien Hsiao

et al.

Aging Cell, Journal Year: 2022, Volume and Issue: 21(11)

Published: Oct. 11, 2022

Abstract There is still a significant lack of knowledge regarding many aspects the etiopathology and consequences severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in humans. For example, variety molecular mechanisms mediating this infection, long‐term disease remain poorly understood. It first seemed like SARS‐CoV‐2 primarily caused serious syndrome. However, over last years, an increasing number studies also pointed towards damaging effects has on central nervous system (CNS). In fact, evidence suggests possible disruption blood–brain barrier deleterious CNS, especially patients who already suffer from other pathologies, such as neurodegenerative disorders. The behind these CNS could involve dysregulation mitochondrial physiology, well‐known early marker neurodegeneration hallmark aging. Moreover, mitochondria are involved activation inflammatory response, which been broadly described COVID‐19. Here, we critically review current bibliography presence symptoms COVID‐19 patients, with special emphasis

Language: Английский

Citations

17
Effect of physical activity on long COVID fatigue: an unsolved enigma DOI Creative Commons

Francesco Coscia,

Ester Sara Di Filippo,

Paola Virginia Gigliotti

et al.

European Journal of Translational Myology, Journal Year: 2023, Volume and Issue: 33(3)

Published: Sept. 4, 2023

Covid-19 disease is well documented and often the most common symptoms include myalgia muscle fatigue. Approximately 10% of those infected complain persistent fatigue even many months after end acute phase disease. This gives rise to a condition different from previous one commonly known as 'post-acute COVID-19 syndrome' or simply Long-COVID. Although origin multifactorial, state prolonged observed in Long-COVID syndrome suggests existence possible atrophy rather sarcopenia. Under these conditions, use physical activity programs can effectively counteract underlying phenomena observed. If this also situation during Long-COVID, muscular symptom should be positively influenced by administration programmed cycles. In fact, patients with few published papers seem indicate that who are physically active make an effort engage illness have decreased duration intensity illness. However, analysis studies literature small percentage people do not appear benefit application programs, so further on homogeneous samples needed provide firm answer question: planned help pathological course Long-COVID?

Language: Английский

Citations

10
Exploring autophagy in treating SARS-CoV-2 spike protein-related pathology DOI Creative Commons
Matthew Halma, Paul E. Marik,

Yusuf M. Saleeby

et al.

Endocrine and Metabolic Science, Journal Year: 2024, Volume and Issue: 14, P. 100163 - 100163

Published: Jan. 30, 2024

Fasting, a practice with historical roots in various cultures, has recently garnered significant interest the field of medicine. In this article, we delve into mechanisms underlying fasting-induced autophagy and its therapeutic applications for spike protein associated pathology. We explore potential fasting on protein-related pathology role interventions to upregulate autophagy, including compounds like spermidine, resveratrol, rapamycin, metformin. conclusion, fasting, coupled an understanding nuances, holds promise as intervention SARS-CoV-2 related diseases; broad implications human health. This review presents possibility using treat diseases, details deploy modality.

Language: Английский

Citations

3
COVID-19 related neurological manifestations in Parkinson’s disease: has ferroptosis been a suspect? DOI Creative Commons
Fengju Jia, Jing Han

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: March 19, 2024

Abstract A rising number of patient cases point to a probable link between SARS-CoV-2 infection and Parkinson’s disease (PD), yet the mechanisms by which affects brain generates neuropsychiatric symptoms in COVID-19 patients remain unknown. Ferroptosis, distinct iron-dependent non-apoptotic type cell death characterized lipid peroxidation glutathione depletion, key factor neurological disorders. Ferroptosis may have pathogenic role COVID-19, according recent findings, however its potential contributions COVID-19-related PD not been investigated. This review covers paths for brain. Among these putative processes, ferroptosis contribute etiology COVID-19-associated PD, potentially providing therapeutic methods.

Language: Английский

Citations

2
Mitochondria in COVID-19: from cellular and molecular perspective DOI Creative Commons
Michał Rurek

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: June 21, 2024

The rapid development of the COVID-19 pandemic resulted in a closer analysis cell functioning during β-coronavirus infection. This review will describe evidence for as syndrome with strong, albeit still underestimated, mitochondrial component. Due to sensitivity host mitochondria coronavirus infection, SARS-CoV-2 affects signaling, modulates immune response, modifies cellular energy metabolism, induces apoptosis and ageing, worsening symptoms which can sometimes be fatal. Various aberrations across human systems tissues their relationships were reported. In this review, particular attention is given characterization multiple alterations gene expression pattern metabolism COVID-19; complexity interactions between proteins presented. participation mitogenome fragments signaling occurrence subgenomic RNA within membranous compartments, including widely discussed. As severely quality system mitochondria, background dynamics additionally characterized. Finally, perspectives on mitigation by affecting biogenesis numerous compounds therapeutic treatments are briefly outlined.

Language: Английский

Citations

2