A Potential Role of the Spike Protein in Neurodegenerative Diseases: A Narrative Review DOI Open Access
Stephanie Seneff, Anthony M. Kyriakopoulos, Greg Nigh

et al.

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 11, 2023

Human prion protein and prion-like misfolding are widely recognized as playing a causal role in many neurodegenerative diseases. Based on vitro vivo experimental evidence relating to disease, we extrapolate from the compelling that spike glycoprotein of SARS-CoV-2 contains extended amino acid sequences characteristic infer its potential cause disease. We propose vaccine-induced synthesis can facilitate accumulation toxic fibrils neurons. outline various pathways through which these proteins could be expected distribute throughout body. review both cellular pathologies expression disease become more frequent those who have undergone mRNA vaccination. Specifically, describe protein’s contributions, via properties, neuroinflammation diseases; clotting disorders within vasculature; further risk due suppressed regulation context prevalent insulin resistance; other health complications. explain why characteristics relevant vaccine-related mRNA-induced than natural infection with SARS-CoV-2. note an optimism apparent loss properties among current Omicron variants. acknowledge chain pathological events described this paper is only hypothetical not yet verified. also usher in, while grounded research literature, currently largely circumstantial, direct. Finally, implications our findings for general public, briefly discuss public recommendations feel need urgent consideration. An earlier version article was previously posted Authorea preprint server August 16, 2022.

Language: Английский

COVID-19-related headache and innate immune response — a narrative review DOI Open Access
Marcin Straburzyński, Ewa Kuca-Warnawin, Marta Waliszewska‐Prosół

et al.

Neurologia i Neurochirurgia Polska, Journal Year: 2022, Volume and Issue: 57(1), P. 43 - 52

Published: June 27, 2022

Language: Английский

Citations

40
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
Long-term effects of SARS-CoV-2 infection on human brain and memory DOI Creative Commons

Qiulu Ding,

H T Zhao

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: June 29, 2023

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused several waves of outbreaks. From the ancestral strain to Omicron variant, SARS-CoV-2 has evolved with high transmissibility and increased immune escape against vaccines. Because multiple basic amino acids in S1-S2 junction spike protein, widespread distribution angiotensin-converting enzyme (ACE2) receptor human body transmissibility, can infect organs led over 0.7 billion infectious cases. Studies showed that infection cause more than 10% patients Long-COVID syndrome, including pathological changes brains. This review mainly provides molecular foundations for understanding mechanism invading brain basis interfering memory, which are associated dysfunction, syncytia-induced cell death, persistence infection, microclots biopsychosocial aspects. We also discuss strategies reducing syndrome. Further studies analysis shared researches will allow further clarity regarding long-term health consequences.

Language: Английский

Citations

29
SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19 DOI Creative Commons
Zhouyi Rong, Hongcheng Mai,

Saketh Kapoor

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 5, 2023

ABSTRACT Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and tissue loss, raising concerns about virus’s potential chronic impact on central nervous system. In this study, we utilized mouse models human post-mortem tissues to investigate presence distribution SARS-CoV-2 spike protein in skull-meninges-brain axis. Our results revealed accumulation skull marrow, meninges, parenchyma. The injection alone cell death brain, highlighting direct effect tissue. Furthermore, observed deceased long after their COVID-19 infection, suggesting that spike’s persistence may contribute long-term symptoms. was neutrophil-related pathways dysregulation proteins involved PI3K-AKT as well complement coagulation pathway. Overall, our findings suggest trafficking from CNS borders into parenchyma identified differentially regulated present insights mechanisms underlying immediate consequences diagnostic therapeutic opportunities. Graphical Summary Short axis presents molecular targets for complications long-COVID-19 patients .

Language: Английский

Citations

25
Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19 DOI Creative Commons
Zhouyi Rong, Hongcheng Mai, Gregor Ebert

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(12), P. 2112 - 2130.e10

Published: Nov. 29, 2024

SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed accumulation of spike protein in skull-meninges-brain axis human COVID-19 patients, persisting long after viral clearance. Further, biomarkers neurodegeneration were elevated cerebrospinal fluid from COVID proteomic analysis skull, meninges, brain samples revealed dysregulated inflammatory pathways neurodegeneration-associated changes. Similar distribution patterns SARS-CoV-2-infected mice. Injection alone was sufficient to induce neuroinflammation, proteome changes axis, anxiety-like behavior, exacerbated outcomes mouse models stroke traumatic injury. Vaccination reduced but did not eliminate Our findings suggest persistent at borders may contribute lasting sequelae COVID-19.

Language: Английский

Citations

10
The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure DOI Creative Commons
Herbert Renz‐Polster, Marie‐Ève Tremblay, Dorothee Bienzle

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: May 9, 2022

Although myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has a specific and distinctive profile of clinical features, the disease remains an enigma because causal explanation pathobiological matrix is lacking. Several potential mechanisms have been identified, including immune abnormalities, inflammatory activation, mitochondrial alterations, endothelial muscular disturbances, cardiovascular anomalies, dysfunction peripheral central nervous systems. Yet, it unclear whether how these pathways may be related orchestrated. Here we explore hypothesis that common denominator processes in ME/CFS system due to impaired or pathologically reactive neuroglia (astrocytes, microglia oligodendrocytes). We will test this by reviewing, reference current literature, two most salient widely accepted features ME/CFS, investigating might linked dysfunctional neuroglia. From review conclude multifaceted pathobiology attributable unifying manner neuroglial dysfunction. Because key – post exertional malaise decreased cerebral blood flow are also recognized subset patients with post-acute sequelae COVID, suggest our findings pertinent entity.

Language: Английский

Citations

35
Activation of TLR4 by viral glycoproteins: A double-edged sword? DOI Creative Commons

Emily A. Halajian,

Emmanuelle V. LeBlanc, Katrina Gee

et al.

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 29, 2022

Recognition of viral infection by pattern recognition receptors is paramount for a successful immune response to infection. However, an unbalanced proinflammatory can be detrimental the host. Recently, multiple studies have identified that SARS-CoV-2 spike protein activates Toll-like receptor 4 (TLR4), resulting in induction cytokine expression. Activation TLR4 glycoproteins has also been observed context other models, including respiratory syncytial virus (RSV), dengue (DENV) and Ebola (EBOV). mechanisms involved virus-TLR4 interactions remained unclear. Here, we review act as pathogen-associated molecular patterns induce via TLR4. We explore current understanding underlying how are recognized discuss contribution activation pathogenesis. identify contentious findings research gaps highlight importance glycoprotein-mediated potential therapeutic approaches.

Language: Английский

Citations

34
The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells DOI Creative Commons
Christopher B. Forsyth, Lijuan Zhang, Abhinav Bhushan

et al.

Microorganisms, Journal Year: 2022, Volume and Issue: 10(10), P. 1996 - 1996

Published: Oct. 10, 2022

The coronavirus disease 2019 (COVID-19) pandemic began in January 2020 Wuhan, China, with a new designated SARS-CoV-2. principal cause of death from COVID-19 quickly emerged as acute respiratory distress syndrome (ARDS). A key ARDS pathogenic mechanism is the "Cytokine Storm", which dramatic increase inflammatory cytokines blood. In last two years pandemic, pathology has some survivors, variety long-term symptoms occur, condition called post-acute sequelae (PASC) or "Long COVID". Therefore, there an urgent need to better understand mechanisms virus. spike protein on surface virus composed joined S1-S2 subunits. Upon S1 binding ACE2 receptor human cells, subunit cleaved and S2 mediates entry then released into blood, might be one pivotal triggers for initiation and/or perpetuation cytokine storm. this study, we tested hypothesis that sufficient activate signaling production, independent Our data support possible role activation production lung intestinal epithelial cells culture. These potential SARS-CoV-2 pathogenesis PASC.

Language: Английский

Citations

33
Toll-Like Receptor Signaling in Severe Acute Respiratory Syndrome Coronavirus 2-Induced Innate Immune Responses and the Potential Application Value of Toll-Like Receptor Immunomodulators in Patients With Coronavirus Disease 2019 DOI Creative Commons
Jiayu Dai, Yibo Wang, Hongrui Wang

et al.

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: June 27, 2022

Toll-like receptors (TLRs) are key sensors that recognize the pathogen-associated molecular patterns (PAMPs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to activate innate immune response clear invading virus. However, dysregulated responses may elicit overproduction proinflammatory cytokines and chemokines, resulting in enhancement immune-mediated pathology. Therefore, a proper understanding interaction between SARS-CoV-2 TLR-induced is very important for development effective preventive therapeutic strategies. In this review, we discuss recognition components by TLRs downstream signaling pathways activated, as well dual role regulating antiviral effects excessive inflammatory patients with disease 2019 (COVID-19). addition, article describes recent progress TLR immunomodulators including agonists antagonists, vaccine adjuvants or agents used treat hyperinflammatory during infection.

Language: Английский

Citations

31
The route of SARS-CoV-2 to brain infection: have we been barking up the wrong tree? DOI Creative Commons
Rafał Butowt, Christopher S. von Bartheld

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: March 15, 2022

This letter draws attention to recent work supporting the notion that SARS-CoV-2 virus may use nervus terminalis rather than olfactory nerve as a shortcut route from nasal cavity infect brain.

Language: Английский

Citations

30