scholarly journals Neurotoxic Amyloidogenic Peptides Identified in the Proteome of SARS-COV2: Potential Implications for Neurological Symptoms in COVID-19

2021 ◽  
Author(s):  
Saba Islam ◽  
Mirren Charnley ◽  
Guneet Bindra ◽  
Julian Ratcliffe ◽  
Jiangtao Zhou ◽  
...  
Keyword(s):  
Memory Loss ◽  
Neuronal Cell ◽  
Neurological Symptoms ◽  
Brain Inflammation ◽  
Peptide Fragments ◽  
Amyloid Aggregates ◽  
The Central Nervous System ◽  
Amyloidogenic Peptides ◽  
Neurological Effects ◽  
Psychiatric Issues

COVID-19 is primarily known as a respiratory disease caused by the virus SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, cognitive and psychiatric issues, severe headaches, and even stroke are reported in as many as 30% of cases and can persist even after the infection is over (so-called 'long COVID'). These neurological symptoms are thought to be caused by brain inflammation, triggered by the virus infecting the central nervous system of COVID-19 patients, however we still don't fully understand the mechanisms for these symptoms. The neurological effects of COVID-19 share many similarities to neurodegenerative diseases such as Alzheimer's and Parkinson's in which the presence of cytotoxic protein-based amyloid aggregates is a common etiological feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we performed a bioinformatic scan of the SARS-CoV-2 proteome, detecting peptide fragments that were predicted to be highly amyloidogenic. We selected two of these peptides and discovered that they do rapidly self-assemble into amyloid. Furthermore, these amyloid assemblies were shown to be highly toxic to a neuronal cell line. We introduce and support the idea that cytotoxic amyloid aggregates of SARS-CoV-2 proteins are causing some of the neurological symptoms commonly found in COVID-19 and contributing to long COVID, especially those symptoms which are novel to long COVID in contrast to other post-viral syndromes.

scholarly journals Neurotoxic Amyloidogenic Peptides in the Proteome of SARS-COV2: Potential Implications for Neurological Symptoms in COVID-19

2022 ◽  
Author(s):  
Mirren Charnley ◽  
Saba Islam ◽  
Guneet Bindra ◽  
Jeremy Engwirda ◽  
Julian Ratcliffe ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Memory Loss ◽  
Neuronal Cell ◽  
Neurological Symptoms ◽  
Open Reading Frame ◽  
Brain Inflammation ◽  
Peptide Fragments ◽  
Reading Frame ◽  
Amyloid Aggregates ◽  
Neurological Effects

Abstract COVID-19 is primarily known as a respiratory disease caused by the virus SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, cognitive and psychiatric issues, severe headaches, and even stroke are reported in as many as 30% of cases and can persist even after the infection is over (so-called ‘long COVID’). These neurological symptoms are thought to be caused by brain inflammation, caused by the virus infecting the central nervous system of COVID-19 patients, however we still don’t understand the molecular mechanisms that trigger these symptoms. The neurological effects of COVID-19 share many similarities to neurodegenerative diseases such as Alzheimer’s and Parkinson’s in which the presence of cytotoxic protein-based amyloid aggregates is a common etiological feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we performed a bioinformatic scan of the SARS-CoV-2 proteome, detecting peptide fragments that were predicted to be highly amyloidogenic. We selected two of these peptides from the open reading frame 6 (ORF6) and open reading frame 10 (ORF10) proteins. The amyloidogenic virus-derived proteins studied in this work did not include spike (S) protein or any other proteins that have been modified to function as antigens in any current vaccines. We discovered that these ORF protein fragments rapidly self-assemble into amyloid aggregates. Furthermore, these amyloid assemblies were shown to be highly toxic to a neuronal cell line. We introduce and support the idea that cytotoxic amyloid aggregates of SARS-CoV-2 proteins are causing some of the neurological symptoms commonly found in COVID-19 and contributing to long COVID.

scholarly journals Testing the Neuroprotective Properties of PCSO-524® Using a Neuronal Cell Cycle Suppression Assay

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 79 ◽  
Author(s):  
Beika Zhu ◽  
Yang Zhang ◽  
Karl Herrup
Keyword(s):  
Cell Cycle ◽  
Neurodegenerative Disease ◽  
Neuronal Cell ◽  
Brain Inflammation ◽  
Neuroprotective Effects ◽  
Ht22 Cells ◽  
Cell Cycle Reentry ◽  
The Central Nervous System ◽  
Vitro Model

Cell cycle reentry is a unified mechanism shared by several neurodegenerative diseases, including Alzheimer’s disease (AD) and Ataxia Telangiectasia (A-T). This phenotype is often related to neuroinflammation in the central nervous system. To mimic brain inflammation in vitro, we adopted the previously established method of using conditioned medium collected from activated THP-1 cells and applied it to both differentiated HT22 cells and primary neurons. Unscheduled cell cycle events were observed in both systems, indicating the potential of this approach as an in vitro model of neurodegenerative disease. We used this assay to measure the neuroprotective effects of New Zealand green-lipped mussel extract, PCSO-524®, to protect post-mitotic cells from cell cycle reentry. We found that, both in vitro and in an animal model, PCSO-524® displayed promising neuroprotective effects, and thus has potential to postpone or prevent the onset of neurodegenerative disease.

scholarly journals Autoimmune encephalitis: clinical spectrum and management

2021 ◽  
pp. practneurol-2020-002567
Author(s):  
Christopher E Uy ◽  
Sophie Binks ◽  
Sarosh R Irani
Keyword(s):  
Patient Outcomes ◽  
Neuronal Cell ◽  
Autoimmune Encephalitis ◽  
Surface Antigens ◽  
Brain Inflammation ◽  
Clinical Experiences ◽  
Cell Surface Antigens ◽  
Neuropsychiatric Diseases ◽  
The Central Nervous System ◽  
Improve Patient

Autoimmune encephalitis defines brain inflammation caused by a misdirected immune response against self-antigens expressed in the central nervous system. It comprises a heterogeneous group of disorders that are at least as common as infectious causes of encephalitis. The rapid and ongoing expansion of this field has been driven by the identification of several pathogenic autoantibodies that cause polysymptomatic neurological and neuropsychiatric diseases. These conditions often show highly distinctive cognitive, seizure and movement disorder phenotypes, making them clinically recognisable. Their early identification and treatment improve patient outcomes, and may aid rapid diagnosis of an underlying associated tumour. Here we summarise the well-known autoantibody-mediated encephalitis syndromes with neuronal cell-surface antigens. We focus on practical aspects of their diagnosis and treatment, offer our clinical experiences of managing such cases and highlight more basic neuroimmunological advances that will inform their future diagnosis and treatments.

The Red Neuronal Pigment in the Nervous System of the Mussel, Mytilus Edulis: Localization and Its Effect on Lateral Ciliary Activity with Spectral and Analytical Changes

1981 ◽  
Vol 39 ◽  
pp. 494-495
Author(s):  
Anthony A. Paparo ◽  
Judith A. Murphy
Keyword(s):  
Nervous System ◽  
Mytilus Edulis ◽  
Neuronal Cell ◽  
Ciliary Activity ◽  
Neuronal Cell Bodies ◽  
The Central Nervous System ◽  
Intracellular Organelles ◽  
The Common ◽  
The Individual ◽  
Cryostat Sections

The purpose of this study was to localize the red neuronal pigment in Mytilus edulis and examine its role in the control of lateral ciliary activity in the gill. The visceral ganglia (Vg) in the central nervous system show an over al red pigmentation. Most red pigments examined in squash preps and cryostat sec tions were localized in the neuronal cell bodies and proximal axon regions. Unstained cryostat sections showed highly localized patches of this pigment scattered throughout the cells in the form of dense granular masses about 5-7 um in diameter, with the individual granules ranging from 0.6-1.3 um in diame ter. Tissue stained with Gomori's method for Fe showed bright blue granular masses of about the same size and structure as previously seen in unstained cryostat sections.Thick section microanalysis (Fig.l) confirmed both the localization and presence of Fe in the nerve cell. These nerve cells of the Vg share with other pigmented photosensitive cells the common cytostructural feature of localization of absorbing molecules in intracellular organelles where they are tightly ordered in fine substructures.

scholarly journals Induced Pluripotent Stem Cell-Derived Neural Precursors Improve Memory, Synaptic and Pathological Abnormalities in a Mouse Model of Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1802
Author(s):  
Enrique Armijo ◽  
George Edwards ◽  
Andrea Flores ◽  
Jorge Vera ◽  
Mohammad Shahnawaz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Memory Loss ◽  
Amyloid Β ◽  
Cerebral Atrophy ◽  
Brain Inflammation ◽  
Neural Precursors ◽  
Model Of Alzheimer’S Disease ◽  
Induced Pluripotent

Alzheimer’s disease (AD) is the most common type of dementia in the elderly population. The disease is characterized by progressive memory loss, cerebral atrophy, extensive neuronal loss, synaptic alterations, brain inflammation, extracellular accumulation of amyloid-β (Aβ) plaques, and intracellular accumulation of hyper-phosphorylated tau (p-tau) protein. Many recent clinical trials have failed to show therapeutic benefit, likely because at the time in which patients exhibit clinical symptoms the brain is irreversibly damaged. In recent years, induced pluripotent stem cells (iPSCs) have been suggested as a promising cell therapy to recover brain functionality in neurodegenerative diseases such as AD. To evaluate the potential benefits of iPSCs on AD progression, we stereotaxically injected mouse iPSC-derived neural precursors (iPSC-NPCs) into the hippocampus of aged triple transgenic (3xTg-AD) mice harboring extensive pathological abnormalities typical of AD. Interestingly, iPSC-NPCs transplanted mice showed improved memory, synaptic plasticity, and reduced AD brain pathology, including a reduction of amyloid and tangles deposits. Our findings suggest that iPSC-NPCs might be a useful therapy that could produce benefit at the advanced clinical and pathological stages of AD.

scholarly journals Detection and Characterization of Autoantibodies to Neuronal Cell-Surface Antigens in the Central Nervous System

2016 ◽  
Vol 9 ◽  
Author(s):  
Marleen H. van Coevorden-Hameete ◽  
Maarten J. Titulaer ◽  
Marco W. J. Schreurs ◽  
Esther de Graaff ◽  
Peter A. E. Sillevis Smitt ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Surface ◽  
Neuronal Cell ◽  
Surface Antigens ◽  
Cell Surface Antigens ◽  
The Central Nervous System

Effect of feeding with bilberry fruit on the expression pattern of αCaMKII in hippocampal neurons in normal and diabetic rats

2017 ◽  
Vol 20 (2) ◽  
pp. 313-319 ◽  
Author(s):  
M. Matysek ◽  
S. Mozel ◽  
R. Szalak ◽  
A. Zacharko-Siembida ◽  
K. Obszańska ◽  
...  
Keyword(s):  
Cognitive Processes ◽  
Hippocampal Neurons ◽  
Negative Impact ◽  
Expression Patterns ◽  
Memory Loss ◽  
Diabetic Rats ◽  
Control Group ◽  
Neuroprotective Effects ◽  
The Central Nervous System ◽  
And Control

Abstract αCaMKII, widely occurring in the central nervous system, plays a significant role in cognitive processes. It is well known that diabetes is a risk factor that may trigger brain atrophy, cognitive dysfunction and finally lead to memory loss. Antioxidants richly present in bilberry fruits are believed to have significant effects on diabetes-related brain dysfunctions mainly due to their abilities to modulate neurotransmitter release that lead to reduction of the negative impact of free radicals on cognitive processes. The aim of the present research was to immunohistochemically investigate the expression patterns of αCaMKII in hippocampal neurons from non-diabetic, diabetic and diabetic rats fed with an extract of bilberry fruit. The obtained results show that in comparison to the control group, in diabetic rats hippocampal neurons immunoreactive (ir) to αCaMKII were swollen and the lengths of the neuronal fibres were reduced. Further study shows that in diabetic rats fed with bilberry fruit, αCaMKII-positive nerve fibres were significantly longer when compared to the groups of diabetic and control rats. Additionally, we observed statistically significant changes in the average larger diameter of αCaMKII-ir hippocampal neurons between groups of diabetic rats (with vs. without supplement of bilberry fruit). The results of the present work suggest that antioxidants present in bilberry fruits influence the morphology of and possibly exhibit beneficial and neuroprotective effects on hippocampal neurons during diabetes. It is likely that changes in the appearance of αCaMKII-expressed hippocampal neurons may reflect the diabetes-evoked rise in Ca2+ level in the cerebral nerve terminals. The present research extends our knowledge of preventive mechanisms for cognitive dysfunctions occurring in the brain during diabetes.

scholarly journals CONTAMINATION BY HEAVY METALS AND ITS CONSEQUENCES: REFLECTIONS

2020 ◽  
Vol 3 (1) ◽  
pp. 101
Author(s):  
Gabrielle Diniz dos Santos ◽  
Gil Dutra Furtado ◽  
Cíntia Cleub Neves Batista
Keyword(s):  
Heavy Metals ◽  
Urban Areas ◽  
Memory Loss ◽  
Trophic Levels ◽  
Low Fertility ◽  
Free Form ◽  
Dissolved Metals ◽  
Physiological Factors ◽  
The Central Nervous System ◽  
Anthropic Influence

Nowadays, the vast majority of aquatic bodies suffer some kind of anthropic influence due to the great expansion of urban areas and consequently industrial areas, with the pollution coming into such environments. One of the types of pollutants present in the environment are heavy metals, which are found naturally in water bodies due to the weathering of rocks and volcanic activities. The present work is of bibliographic nature, based on searches in the bibliography pertinent to the theme. It is possible to state that with anthropic intervention, such metals become common and are found in greater quantities in the environment in a free form. Thus, some of the most common sources of release of heavy metals into the environment are fertilizers, pesticides, coal and oil combustion, vehicular emissions, mining, smelting, refinement and incineration of urban and industrial waste. Thus making contamination of humans with heavy metals more and more common, one of the most common and easy forms of contamination is through food. The absorption of metals by animals can occur in two ways, bioaccumulation and biomagnification. The first occurs through the diffusion or ingestion of the dissolved metals in the water, which occur through the gills or the digestive tract and then lodges in the animals' tissues, so that the organism cannot absorb it, thus obtaining a bioaccumulative character. In the trophic biomagnification or magnification, the concentration of metals in the organism occurs gradually through the trophic levels. The transfer of contaminants through the food chain characterizes such a process that passes from producers to consumers and the longer the chain, the greater the concentration on the final consumer. Therefore, we can emphasize that the concentration and absorption content of such substances are relative and depend on several environmental and physiological factors that vary between species of beings. Metal poisoning can cause serious damage, such as low fertility, decreased immune defenses, reduced growth rate and pathologies that can lead to senescence. Metals can cause different problems in humans, most of which are of a motor nature, as they directly affect the central nervous system (CNS), and can cause memory loss, uncontrolled limb tremors, muscle atrophy, kidney injuries, among others.

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