Peripheral Pathways to Neurovascular Unit Dysfunction, Cognitive Impairment, and Alzheimer’s Disease DOI Creative Commons
Amy R. Nelson

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: April 18, 2022

Alzheimer's disease (AD) is the most common form of dementia. It was first described more than a century ago, and scientists are acquiring new data learning novel information about every day. Although there nuances details continuously being unraveled, many key players were identified in early 1900's by Dr. Oskar Fischer Alois Alzheimer, including amyloid-beta (Aβ), tau, vascular abnormalities, gliosis, possible role infections. More recently, has been growing interest appreciation for neurovascular unit dysfunction that occurs mild cognitive impairment (MCI) before independent Aβ tau brain accumulation. In last decade, evidence oligomers antimicrobial peptides generated response to infection expanded our knowledge challenged preconceived notions. The concept pathogenic germs cause infections generating an innate immune (e.g., produced peripheral organs) associated with incident dementia worthwhile considering context sporadic AD unknown root cause. Therefore, amyloid hypothesis proposed remains be vetted future research. Meanwhile, humans remain complex variable organisms individual risk factors define their status, function, neuronal plasticity. this focused review, idea organ contribute disease, through generation amyloids and/or will explored discussed. Ultimately, questions answered critical areas exploration highlighted.

Language: Английский

Recombinant SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Stimulate Release of Different Pro-Inflammatory Mediators via Activation of Distinct Receptors on Human Microglia Cells DOI Open Access
Irene Tsilioni, Theoharis C. Theoharides

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 60(11), P. 6704 - 6714

Published: July 21, 2023

Language: Английский

Citations

16
SARS-CoV-2 and Multiple Sclerosis: Potential for Disease Exacerbation DOI Creative Commons
Madison MacDougall,

Jad El-Hajj Sleiman,

Philippe Beauchemin

et al.

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

Published: April 22, 2022

While the respiratory tract is primary route of entry for SARS-CoV-2, evidence shows that virus also impacts central nervous system. Intriguingly, case reports have documented SARS-CoV-2 patients presenting with demyelinating lesions in brain, spinal cord, and optic nerve, suggesting possible implications neuroimmune disorders such as multiple sclerosis (MS) other related disorders. However, cellular mechanisms underpinning these observations remain poorly defined. The goal this paper was to review literature date regarding links between infection diseases MS its disorders, aim positing a hypothesis disease exacerbation. suggests SARS-CoV, orthologous murine coronaviruses invade CNS via olfactory bulb, spreading connected structures retrograde transport. We hypothesize glial inflammatory response may contribute damaged oligodendrocytes blood brain barrier (BBB) breakdown, allowing second invasion lymphocyte infiltration. Potential molecular mimicry stimulation autoreactive T cells against myelin described. It imperative further studies on neuroinvasion address adverse effects exacerbation symptoms, nearly 3 million people suffer from worldwide.

Language: Английский

Citations

20
Mechanisms by Which SARS-CoV-2 Invades and Damages the Central Nervous System: Apart from the Immune Response and Inflammatory Storm, What Else Do We Know? DOI Creative Commons
Zihan Sun,

Chunying Shi,

Lixin Jin

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(5), P. 663 - 663

Published: April 24, 2024

Initially reported as pneumonia of unknown origin, COVID-19 is increasingly being recognized for its impact on the nervous system, despite system invasions extremely rare. As a result, numerous studies have been conducted to elucidate mechanisms damage and propose appropriate coping strategies. This review summarizes by which SARS-CoV-2 invades damages central with specific focus aspects apart from immune response inflammatory storm. The latest research findings these are presented, providing new insights further in-depth research.

Language: Английский

Citations

4
Postinfectious Pulmonary Complications: Establishing Research Priorities to Advance the Field: An Official American Thoracic Society Workshop Report DOI
Sara C. Auld, Ajay Sheshadri, Jennifer Alexander‐Brett

et al.

Annals of the American Thoracic Society, Journal Year: 2024, Volume and Issue: 21(9), P. 1219 - 1237

Published: July 25, 2024

Continued improvements in the treatment of pulmonary infections have paradoxically resulted a growing challenge individuals with postinfectious complications (PIPCs). PIPCs been long recognized after tuberculosis, but recent experiences such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic underscored importance following other lower tract infections. Independent causative pathogen, most available studies focus on short-term outcomes rather than long-term morbidity among survivors. In this document, we establish conceptual scope for discussion globally significant pathogens and an examination how these can damage different components lung, resulting spectrum PIPCs. We also review potential mechanisms transition from infection to PIPC, including interplay between pathogen-mediated injury aberrant host responses, which together result Finally, identify cross-cutting research priorities field facilitate future incidence PIPCs, define common mechanisms, therapeutic strategies, ultimately reduce burden survivors

Language: Английский

Citations

4
Acute and long-term effects of COVID-19 on brain and mental health: A narrative review DOI
J. Douglas Bremner, Scott J. Russo,

Richard J. Gallagher

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 123, P. 928 - 945

Published: Nov. 3, 2024

Language: Английский

Citations

4
The influence of SARS-CoV-2 spike protein exposure on retinal development in the human retinal organoids DOI Creative Commons
Jing Gong, Lingling Ge, Yuxiao Zeng

et al.

Cell & Bioscience, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 11, 2025

Abstract Background Pregnant women are considered a high-risk population for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as the virus can infect placenta and embryos. Recently, SARS-CoV-2 has been widely reported to cause retinal pathological changes embryonic retina. The infection of host cells by is primarily mediated through spike (S) protein, which also plays crucial role in pathogenesis SARS-CoV-2. However, it remains poorly understood how S protein affects development, underlying mechanism not yet clarified. Methods We used human stem cell-derived organoids (hEROs) model study effect exposure at different stages development. hEROs were treated with μg/mL on days 90 280. Immunofluorescence staining, RNA sequencing, RT-PCR performed assess influence development both early late stages. Results results showed that ACE2 TMPRSS2, receptors facilitating entry into cells, expressed hEROs. Exposure induced an inflammatory response Additionally, sequencing indicated affected nuclear components lipid metabolism, while late-stages resulted cell membrane extracellular matrix. Conclusion This work highlights differential effects stages, providing insights cellular molecular mechanisms SARS-CoV-2-induced developmental impairments

Language: Английский

Citations

0
Spike protein-related proteinopathies: a focus on the neurological side of spikeopathies DOI Creative Commons
Andreas Posa

Annals of Anatomy - Anatomischer Anzeiger, Journal Year: 2025, Volume and Issue: unknown, P. 152662 - 152662

Published: April 1, 2025

Language: Английский

Citations

0
Vascular dysfunction in COVID-19 patients: update on SARS-CoV-2 infection of endothelial cells and the role of long non-coding RNAs DOI Creative Commons
Jaroslav Pelisek, Benedikt Reutersberg, Urs F. Greber

et al.

Clinical Science, Journal Year: 2022, Volume and Issue: 136(21), P. 1571 - 1590

Published: Nov. 1, 2022

Abstract Although COVID-19 is primarily a respiratory disease, it may affect also the cardiovascular system. patients with disorder (CVD) develop more severe disease course significantly higher mortality rate than non-CVD patients. A common denominator of CVD dysfunction endothelial cells (ECs), increased vascular permeability, endothelial-to-mesenchymal transition, coagulation, and inflammation. It has been assumed that clinical complications in suffering from are caused by SARS-CoV-2 infection ECs through angiotensin-converting enzyme 2 (ACE2) receptor cellular transmembrane protease serine (TMPRSS2) consequent infected cells. Meanwhile, other factors associated entry into host have described, including disintegrin metalloproteinase domain-containing protein 17 (ADAM17), C-type lectin CD209L or heparan sulfate proteoglycans (HSPG). Here, we discuss current data about putative smooth muscle Furthermore, highlight potential role long non-coding RNAs (lncRNAs) affecting permeability CVD, process might exacerbate

Language: Английский

Citations

17
An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection DOI Creative Commons
Christian Devaux, Laurence Camoin‐Jau

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

Published: Nov. 28, 2022

It has been known for many years that the angiotensin-converting enzyme 2 (ACE2) is a cell surface involved in regulation of blood pressure. More recently, it was proven severe acute respiratory syndrome coronavirus (SARS-CoV-2) interacts with ACE2 to enter susceptible human cells. This functional duality tends explain why this molecule plays such an important role clinical manifestations disease 2019 (COVID-19). At very start pandemic, publication from our Institute (entitled "ACE2 receptor polymorphism: susceptibility SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 outcome"), one first reviews linking duplicitous nature ACE2. However, even given pathophysiology may be driven by imbalance renin-angiotensin system (RAS), we were still far understanding complexity mechanisms which are controlled different types. To gain insight into physiopathology SARS-CoV-2 infection, essential consider polymorphism expression levels gene (including its alternative isoforms). Over past years, impressive amount new results have come shed light on COVID-19, requiring us update analysis. Genetic linkage studies reported highlight relationship between genetic variants risk developing hypertension. Currently, research efforts being undertaken understand links severity COVID-19. In review, state knowledge consequences individuals SARS-CoV-2. We also discuss link increase angiotensin II among SARS-CoV-2-infected patients development cytokine storm associated microvascular injury obstructive thrombo-inflammatory syndrome, represent primary causes forms lethality. Finally, summarize therapeutic strategies aimed at preventing target Changing paradigms help improve patients' therapy.

Language: Английский

Citations

17
Brain pericyte biology: from physiopathological mechanisms to potential therapeutic applications in ischemic stroke DOI Creative Commons
Jiaqi Fu, Huazheng Liang, Ping Yuan

et al.

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

Published: Sept. 14, 2023

Pericytes play an indispensable role in various organs and biological processes, such as promoting angiogenesis, regulating microvascular blood flow, participating immune responses. Therefore, this review, we will first introduce the discovery development of pericytes, identification methods functional characteristics, then focus on brain one hand, to summarize functions pericytes under physiological conditions, mainly discussing from aspects stem cell contractile characteristics paracrine characteristics; other pathological taking ischemic stroke example. Finally, discuss analyze application therapeutic targets, providing research basis direction for future diseases, especially treatment.

Language: Английский

Citations

10