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

Understanding COVID-19-associated coagulopathy DOI Open Access
Edward M. Conway, Nigel Mackman, Ronald Q. Warren

et al.

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 22(10), P. 639 - 649

Published: Aug. 5, 2022

Language: Английский

Citations

252
Adverse effects of COVID-19 mRNA vaccines: the spike hypothesis DOI
Ioannis P. Trougakos, Evangelos Terpos, Harry Alexopoulos

et al.

Trends in Molecular Medicine, Journal Year: 2022, Volume and Issue: 28(7), P. 542 - 554

Published: April 21, 2022

Language: Английский

Citations

202
SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice DOI Creative Commons
Fabrícia Lima Fontes-Dantas, Gabriel Gripp Fernandes,

Elisa Gouvea Gutman

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(3), P. 112189 - 112189

Published: Feb. 17, 2023

Cognitive dysfunction is often reported in patients with post-coronavirus disease 2019 (COVID-19) syndrome, but its underlying mechanisms are not completely understood. Evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein or fragments released from cells during infection, reaching different tissues, including the CNS, irrespective of presence viral RNA. Here, we demonstrate brain infusion mice has a late impact on cognitive function, recapitulating post-COVID-19 syndrome. We also show neuroinflammation and hippocampal microgliosis mediate Spike-induced memory via complement-dependent engulfment synapses. Genetic pharmacological blockage Toll-like receptor 4 (TLR4) signaling protects animals against synapse elimination induced by infusion. Accordingly, cohort 86 who recovered mild COVID-19, genotype GG TLR4-2604G>A (rs10759931) associated poor outcome. These results identify TLR4 as key target to investigate long-term after COVID-19 infection humans rodents.

Language: Английский

Citations

107
Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches DOI Creative Commons
Jasimuddin Ahamed, Jeffrey Laurence

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(15)

Published: July 31, 2022

SARS-CoV-2–infected individuals may suffer a multi–organ system disorder known as "long COVID" or post-acute sequelae of SARS-CoV-2 infection (PASC). There are no standard treatments, the pathophysiology is unknown, and incidence varies by clinical phenotype. Acute COVID-19 correlates with biomarkers systemic inflammation, hypercoagulability, comorbidities that less prominent in PASC. Macrovessel thrombosis, hallmark acute COVID-19, frequent Female sex at birth associated reduced risk for progression, but increased Persistent microvascular endotheliopathy cryptic tissue reservoirs has been implicated PASC pathology. Autoantibodies, localized reactivation latent pathogens also be involved, potentially leading to documented multiple tissues. Diagnostic assays illuminating possible therapeutic targets discussed.

Language: Английский

Citations

103
Neuroinflammation and COVID-19 DOI Creative Commons
Abigail Vanderheiden, Robyn S. Klein

Current Opinion in Neurobiology, Journal Year: 2022, Volume and Issue: 76, P. 102608 - 102608

Published: June 29, 2022

Coronavirus disease 2019 (COVID-19) has caused a historic pandemic of respiratory disease. COVID-19 also causes acute and post-acute neurological symptoms, which range from mild, such as headaches, to severe, including hemorrhages. Current evidence suggests that there is no widespread infection the central nervous system (CNS) by SARS-CoV-2, thus what causing disease? Here, we review potential immunological mechanisms driving in patients. We begin discussing implications imbalanced peripheral immunity on CNS function. Next, examine for dysregulation blood-brain barrier during SARS-CoV-2 infection. Last, discuss role myeloid cells may play promoting Combined, highlight innate neuroinflammation suggest areas future research.

Language: Английский

Citations

82
Long-Term Outcomes of Pediatric Infections: From Traditional Infectious Diseases to Long Covid DOI Creative Commons
Danilo Buonsenso, Leonardo Di Gennaro, Cristina De Rose

et al.

Future Microbiology, Journal Year: 2022, Volume and Issue: 17(7), P. 551 - 571

Published: March 10, 2022

There is limited evidence available on the long-term impact of SARS-CoV-2 infection in children. In this article, authors analyze recent pediatric long Covid and lessons learnt from a post-Covid unit Rome, Italy. To gain better understanding concerns raised by parents physicians relation to potential consequences novel infection, it important recognize that effect post-infectious disease not new phenomenon.

Language: Английский

Citations

81
PANoptosis: Mechanisms, biology, and role in disease DOI Open Access

Xu Sun,

Yanpeng Yang,

Xiaona Meng

et al.

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 246 - 262

Published: Oct. 12, 2023

Summary Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which mediated by multifaceted PANoptosome complexes assembled via integrating components from other modalities. There growing interest in process function of PANoptosis. Accumulating evidence suggests that occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, cancer. Given impact across disease spectrum, this review briefly describes relationships highlights key molecules formation activation, outlines roles diseases together with potential therapeutic targeting. We also discuss important concepts pressing issues future research. Improved understanding its mechanisms crucial identifying novel targets strategies.

Language: Английский

Citations

69
Role of SARS-CoV-2 Spike-Protein-Induced Activation of Microglia and Mast Cells in the Pathogenesis of Neuro-COVID DOI Creative Commons
Theoharis C. Theoharides, Duraisamy Kempuraj

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 688 - 688

Published: Feb. 22, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes disease 2019 (COVID-19). About 45% of COVID-19 patients experience several symptoms a few months after the initial infection and develop post-acute sequelae SARS-CoV-2 (PASC), referred to as “Long-COVID,” characterized by persistent physical mental fatigue. However, exact pathogenetic mechanisms affecting brain are still not well-understood. There is increasing evidence neurovascular inflammation in brain. precise role neuroinflammatory response that contributes severity long COVID pathogenesis clearly understood. Here, we review reports spike protein can cause blood–brain barrier (BBB) dysfunction damage neurons either directly, or via activation mast cells microglia release various molecules. Moreover, provide recent novel flavanol eriodictyol particularly suited for development an effective treatment alone together with oleuropein sulforaphane (ViralProtek®), all which have potent anti-viral anti-inflammatory actions.

Language: Английский

Citations

53
Innate immune sensors and regulators at the blood brain barrier: focus on toll-like receptors and inflammasomes as mediators of neuro-immune crosstalk and inflammation DOI Creative Commons
Çiğdem Acıoğlu, Stella Elkabes

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 15, 2025

Cerebral endothelial cells (CEC) that form the brain capillaries are principal constituents of blood barrier (BBB), main active interface between and which plays a protective role by restricting infiltration pathogens, harmful substances immune into while allowing entry essential nutrients. Aberrant CEC function often leads to increased permeability BBB altering bidirectional communication bloodstream facilitating extravasation brain. In addition their as gatekeepers BBB, exhibit cell properties they can receive transmit signals partly via release inflammatory effectors in pathological conditions. express innate receptors, including toll like receptors (TLRs) inflammasomes first sensors exogenous or endogenous dangers initiators responses drive neural dysfunction degeneration. Accumulating evidence indicates activation TLRs compromises integrity, promotes aberrant neuroimmune interactions modulates both systemic neuroinflammation, common features neurodegenerative psychiatric diseases central nervous system (CNS) infections injuries. The goal present review is provide an overview pivotal roles played discuss molecular cellular mechanisms contribute disruption neuroinflammation especially context traumatic ischemic injuries infections. We will focus on most recent advances literature reports field highlight knowledge gaps. future research directions advance our understanding contribution potential at promising therapeutic targets wide variety conditions

Language: Английский

Citations

3
The COVID-19 pandemic and Alzheimer’s disease: mutual risks and mechanisms DOI Creative Commons
Feng Chen, Yan‐Ting Chen, Yongxiang Wang

et al.

Translational Neurodegeneration, Journal Year: 2022, Volume and Issue: 11(1)

Published: Sept. 11, 2022

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a life-threatening disease, especially in elderly individuals and those with comorbidities. The predominant clinical manifestation of COVID-19 dysfunction, while neurological presentations are increasingly being recognized. SARS-CoV-2 invades host cells primarily via attachment the spike protein to angiotensin-converting enzyme (ACE2) receptor expressed on cell membranes. Patients Alzheimer's (AD) more susceptible infection prone outcomes. Recent studies have revealed some common risk factors for AD COVID-19. An understanding association between potential related mechanisms may lead development novel approaches treating both diseases. In present review, we first summarize central nervous system (CNS) then discuss associations shared key AD, focus ACE2 receptor, apolipoprotein E (APOE) genotype, age, neuroinflammation.

Language: Английский

Citations

45