Investigating the Potential Shared Molecular Mechanisms between COVID-19 and Alzheimer’s Disease via Transcriptomic Analysis DOI Creative Commons
Yixian Fan, Xiaozhao Liu, Fei Guan

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(1), P. 100 - 100

Published: Jan. 9, 2024

SARS-CoV-2 caused the COVID-19 pandemic. may elevate risk of cognitive impairment and even cause dementia in infected individuals; it accelerate decline elderly patients with dementia, possibly Alzheimer's disease (AD) patients. However, mechanisms underlying interplay between AD are still unclear. To investigate associations progression infection, we conducted a series bioinformatics research into SARS-CoV-2-infected cells, patients, We identified common differentially expressed genes (DEGs) these DEGs enriched certain pathways, such as immune responses cytokine storms. constructed gene interaction network signaling transduction module center

Language: Английский

Biological age is increased by stress and restored upon recovery DOI
Jesse R. Poganik, Bohan Zhang, Gurpreet S. Baht

et al.

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(5), P. 807 - 820.e5

Published: April 21, 2023

Language: Английский

Citations

141
SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence DOI Creative Commons
Ubaldo Gioia, Sara Tavella, Pamela Martínez-Orellana

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(4), P. 550 - 564

Published: March 9, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the RNA virus responsible for disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 was reported to alter several cellular pathways, its impact on DNA integrity and mechanisms involved remain unknown. Here we show that causes damage elicits an altered response. Mechanistically, proteins ORF6 NSP13 cause degradation of response kinase CHK1 through proteasome autophagy, respectively. loss leads deoxynucleoside triphosphate (dNTP) shortage, causing impaired S-phase progression, damage, pro-inflammatory pathways activation senescence. Supplementation deoxynucleosides reduces that. Furthermore, N-protein impairs 53BP1 focal recruitment by interfering with damage-induced long non-coding RNAs, thus reducing repair. Key observations are recapitulated in SARS-CoV-2-infected mice patients COVID-19. We propose SARS-CoV-2, boosting ribonucleoside levels promote replication at expense dNTPs hijacking RNAs' biology, threatens genome activation, induction inflammation

Language: Английский

Citations

78
Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19 DOI
Josefine Radke, Jenny Meinhardt, Tom Aschman

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(3), P. 409 - 420

Published: Feb. 16, 2024

Language: Английский

Citations

34
Widespread white matter oedema in subacute COVID-19 patients with neurological symptoms DOI Open Access
Alexander Rau,

Nils Schroeter,

Ganna Blazhenets

et al.

Brain, Journal Year: 2022, Volume and Issue: 145(9), P. 3203 - 3213

Published: Feb. 4, 2022

Abstract While neuropathological examinations in patients who died from COVID-19 revealed inflammatory changes cerebral white matter, MRI frequently fails to detect abnormalities even the presence of neurological symptoms. Application multi-compartment diffusion microstructure imaging (DMI), that detects small volume shifts between compartments (intra-axonal, extra-axonal and free water/CSF) a matter model, is promising approach overcome this discrepancy. In monocentric prospective study, cohort 20 inpatients (57.3 ± 17.1 years) with symptoms (e.g. delirium, cranial nerve palsies) cognitive impairments measured by Montreal Cognitive Assessment (MoCA test; 22.4 4.9; 70% below cut-off value <26/30 points) underwent DMI subacute stage disease (29.3 14.8 days after positive PCR). A comparison whole-brain parameters matched healthy control group (n = 35) shift intra- space into water fraction (V-CSF). This widespread COVID-related V-CSF increase affected entire supratentorial maxima frontal parietal regions. Streamline-wise comparisons controls further network most fibres connecting cortical regions all lobes. The magnitude these (V-CSF) was associated impairment MoCA test (r −0.64, P 0.006) but not olfactory performance 0.29, 0.12). Furthermore, non-significant trend for an association interleukin-6 emerged 0.48, 0.068), prominent marker related response. 14/20 also received 18F-FDG PET, expression previously defined COVID-19-related metabolic spatial covariance pattern 0.57; 0.039). addition, frontoparietal-dominant neocortical glucose hypometabolism well focus increase. summary, compatible vasogenic oedema, affecting various tracts. These were PET imaging.

Language: Английский

Citations

48
The neurobiology of SARS-CoV-2 infection DOI
Jenny Meinhardt,

Simon Streit,

Carsten Dittmayer

et al.

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 25(1), P. 30 - 42

Published: Dec. 4, 2023

Language: Английский

Citations

35
Effect of peripheral cellular senescence on brain aging and cognitive decline DOI Creative Commons

Vivekananda Budamagunta,

Ashok Kumar, Asha Rani

et al.

Aging Cell, Journal Year: 2023, Volume and Issue: 22(5)

Published: March 23, 2023

Abstract We examine similar and differential effects of two senolytic treatments, ABT‐263 dasatinib + quercetin (D Q), in preserving cognition, markers peripheral senescence, brain aging thought to underlie cognitive decline. Male F344 rats were treated from 12 18 months age with D Q, ABT‐263, or vehicle, compared young (6 months). Both treatments rescued memory, preserved the blood–brain barrier (BBB) integrity, prevented age‐related decline hippocampal N‐methyl‐D‐aspartate receptor (NMDAR) function associated impaired cognition. Senolytic decreased senescence‐associated secretory phenotype (SASP) inflammatory cytokines/chemokines plasma (IL‐1β, IP‐10, RANTES), some more responsive Q (TNFα) (IFNγ, leptin, EGF). was effective decreasing senescence genes spleen. expression immune response oxidative stress increased synaptic dentate gyrus (DG). However, influenced twice as many ABT‐263. Relative group exhibited DG linked cell death negative regulation apoptosis microglial activation. Furthermore, at morphological The results indicate that cognition removal senescent cells, systemic inflammation normally drives neuroinflammation, BBB breakdown, function. Dissimilarities transcription divergence central mechanisms, possibly due access.

Language: Английский

Citations

34
Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology DOI Creative Commons
Julio Aguado, Alberto A. Amarilla, Atefeh Taherian Fard

et al.

Nature Aging, Journal Year: 2023, Volume and Issue: 3(12), P. 1561 - 1575

Published: Nov. 13, 2023

Aging is a major risk factor for neurodegenerative diseases, and coronavirus disease 2019 (COVID-19) linked to severe neurological manifestations. Senescent cells contribute brain aging, but the impact of virus-induced senescence on neuropathologies unknown. Here we show that senescent accumulate in aged human organoids senolytics reduce age-related inflammation rejuvenate transcriptomic aging clocks. In postmortem brains patients with COVID-19 observed increased cell accumulation compared age-matched controls. Exposure acute respiratory syndrome 2 (SARS-CoV-2) induced cellular senescence, analysis revealed unique SARS-CoV-2 inflammatory signature. Senolytic treatment infected blocked viral replication prevented distinct neuronal populations. human-ACE2-overexpressing mice, improved clinical outcomes, promoted dopaminergic neuron survival alleviated proinflammatory gene expression. Collectively our results demonstrate an important role driving SARS-CoV-2-induced neuropathology, therapeutic benefit senolytic treatments.

Language: Английский

Citations

31
Sequential multi-omics analysis identifies clinical phenotypes and predictive biomarkers for long COVID DOI Creative Commons
Kaiming Wang,

Mobin Khoramjoo,

Karthik K. Srinivasan

et al.

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(11), P. 101254 - 101254

Published: Oct. 26, 2023

The post-acute sequelae of COVID-19 (PASC), also known as long COVID, is often associated with debilitating symptoms and adverse multisystem consequences. We obtain plasma samples from 117 individuals during 6 months following their acute phase infection to comprehensively profile assess changes in cytokines, proteome, metabolome. Network analysis reveals sustained inflammatory response, platelet degranulation, cellular activation convalescence accompanied by dysregulation arginine biosynthesis, methionine metabolism, taurine tricarboxylic acid (TCA) cycle processes. Furthermore, we develop a prognostic model composed 20 molecules involved regulating T cell exhaustion energy metabolism that can reliably predict clinical outcomes discharge 83% accuracy an area under the curve (AUC) 0.96. Our study pertinent biological processes differ infection, it supports development specific therapies biomarkers for patients suffering COVID.

Language: Английский

Citations

27
Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms DOI Open Access
Ann‐Charlotte Granholm

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(9), P. 3190 - 3190

Published: April 28, 2023

Numerous investigations have demonstrated significant and long-lasting neurological manifestations of COVID-19. It has been suggested that as many four out five patients who sustained COVID-19 will show one or several symptoms can last months after the infection run its course. Neurological are most common in people less than 60 years age, while encephalopathy is more those over 60. Biological mechanisms for these need to be investigated may include both direct indirect effects virus on brain spinal cord. Individuals with Alzheimer’s disease (AD) related dementia, well persons Down syndrome (DS), especially vulnerable COVID-19, but biological reasons this not clear. Investigating consequences an urgent emerging medical need, since close 700 million worldwide now had at least once. likely there a new burden healthcare economy dealing long-term severe SARS-CoV-2 infections long COVID, even younger generations. Interestingly, acute strikingly similar observed mild traumatic injury (mTBI) concussion, including dizziness, balance issues, anosmia, headaches. The possible convergence pathways involved discussed. current review focused commonly described symptoms, molecular involved.

Language: Английский

Citations

24
Gut-brain pathogenesis of post-acute COVID-19 neurocognitive symptoms DOI Creative Commons

Allison M. Plummer,

Yvette L. Matos,

Henry C. Lin

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Sept. 28, 2023

Approximately one third of non-hospitalized coronavirus disease 2019 (COVID-19) patients report chronic symptoms after recovering from the acute stage severe respiratory syndrome 2 (SARS-CoV-2) infection. Some most persistent and common complaints this post-acute COVID-19 (PACS) are cognitive in nature, described subjectively as “brain fog” also objectively measured deficits executive function, working memory, attention, processing speed. The mechanisms these sequelae currently not understood. SARS-CoV-2 inflicts damage to cerebral blood vessels intestinal wall by binding angiotensin-converting enzyme (ACE2) receptors evoking production high levels systemic cytokines, compromising brain’s neurovascular unit, degrading barrier, potentially increasing permeability both harmful substances. Such substances hypothesized be produced gut pathogenic microbiota that, given profound effects has on gastrointestinal system, may fourish a result post-COVID-19 dysbiosis. therefore create scenario which neurotoxic neuroinflammatory readily proliferate lumen encounter weakened gaining access brain subsequently producing deficits. Here, we review proposed PACS pathogenesis along gut-brain axis, while identifying specific methodologies that available experimentally measure each individual component model.

Language: Английский

Citations

23