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 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 Neuronal Cell-type Engineering by Transcriptional Activation

2021 ◽  
Vol 3 ◽  
Author(s):  
Songlei Liu ◽  
Johannes Striebel ◽  
Giovanni Pasquini ◽  
Alex H. M. Ng ◽  
Parastoo Khoshakhlagh ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Recent Progress ◽  
Gene Activation ◽  
Neuronal Cell ◽  
Open Reading Frame ◽  
Cell Type ◽  
Reading Frame ◽  
Cellular Behavior ◽  
Technical Parameters

Gene activation with the CRISPR-Cas system has great implications in studying gene function, controlling cellular behavior, and modulating disease progression. In this review, we survey recent studies on targeted gene activation and multiplexed screening for inducing neuronal differentiation using CRISPR-Cas transcriptional activation (CRISPRa) and open reading frame (ORF) expression. Critical technical parameters of CRISPRa and ORF-based strategies for neuronal programming are presented and discussed. In addition, recent progress on in vivo applications of CRISPRa to the nervous system are highlighted. Overall, CRISPRa represents a valuable addition to the experimental toolbox for neuronal cell-type programming.

scholarly journals The pro1+ Gene From Sordaria macrospora Encodes a C6 Zinc Finger Transcription Factor Required for Fruiting Body Development

Genetics ◽  
1999 ◽  
Vol 152 (1) ◽  
pp. 191-199 ◽  
Author(s):  
Sandra Masloff ◽  
Stefanie Pöggeler ◽  
Ulrich Kück
Keyword(s):  
Zinc Finger ◽  
Fruiting Body ◽  
Molecular Mechanisms ◽  
Developmental Process ◽  
Open Reading Frame ◽  
Cosmid Library ◽  
Reading Frame ◽  
Sordaria Macrospora ◽  
Body Development ◽  
Fruiting Body Development

Abstract During sexual morphogenesis, the filamentous ascomycete Sordaria macrospora differentiates into multicellular fruiting bodies called perithecia. Previously it has been shown that this developmental process is under polygenic control. To further understand the molecular mechanisms involved in fruiting body formation, we generated the protoperithecia forming mutant pro1, in which the normal development of protoperithecia into perithecia has been disrupted. We succeeded in isolating a cosmid clone from an indexed cosmid library, which was able to complement the pro1- mutation. Deletion analysis, followed by DNA sequencing, subsequently demonstrated that fertility was restored to the pro1 mutant by an open reading frame encoding a 689-amino-acid polypeptide, which we named PRO1. A region from this polypeptide shares significant homology with the DNA-binding domains found in fungal C6 zinc finger transcription factors, such as the GAL4 protein from yeast. However, other typical regions of C6 zinc finger proteins, such as dimerization elements, are absent in PRO1. The involvement of the pro1+ gene in fruiting body development was further confirmed by trying to complement the mutant phenotype with in vitro mutagenized and truncated versions of the pro1 open reading frame. Southern hybridization experiments also indicated that pro1+ homologues are present in other sexually propagating filamentous ascomycetes.

scholarly journals Herpesvirus Saimiri Open Reading Frame 50 (Rta) Protein Reactivates the Lytic Replication Cycle in a Persistently Infected A549 Cell Line

2001 ◽  
Vol 75 (8) ◽  
pp. 4008-4013 ◽  
Author(s):  
Delyth J. Goodwin ◽  
Matthew S. Walters ◽  
Peter G. Smith ◽  
Mathias Thurau ◽  
Helmut Fickenscher ◽  
...  
Keyword(s):  
Cell Line ◽  
A549 Cell ◽  
Molecular Mechanisms ◽  
Lytic Replication ◽  
Replication Cycle ◽  
Open Reading Frame ◽  
Herpesvirus Saimiri ◽  
A549 Cell Line ◽  
Reading Frame ◽  
Virus Recovery

ABSTRACT Herpesviruses occur in two distinct forms of infection, lytic replication and latent persistence. In this study, we investigated the molecular mechanisms that govern the latent-lytic switch in the prototype gamma-2 herpesvirus, herpesvirus saimiri (HVS). We utilized a persistently HVS-infected A549 cell line, in which HVS DNA is stably maintained as nonintegrated circular episomes, to assess the role of the open reading frame 50 (ORF 50) (Rta) proteins in the latent-lytic switch. Northern blot analysis and virus recovery assays determined that the ORF 50a gene product, when expressed under the control of a constitutively active promoter, was sufficient to reactivate the entire lytic replication cycle, producing infectious virus particles. Furthermore, although the ORF 50 proteins of HVS strains A11 and C488 are structurally divergent, they were both capable of inducing the lytic replication cycle in this model of HVS latency.

Lighting a path: genetic studies pinpoint neurodevelopmental mechanisms in autism and related disorders

2012 ◽  
Vol 14 (3) ◽  
pp. 239-252
Keyword(s):  
Molecular Mechanisms ◽  
Protein Localization ◽  
Regulation Of Gene Expression ◽  
Neuronal Cell ◽  
Mrna Splicing ◽  
Genetic Mutations ◽  
Scaffolding Proteins ◽  
Molecular Processes ◽  
Genetic Studies ◽  
Novel Treatments

In this review, we outline critical molecular processes that have been implicated by discovery of genetic mutations in autism. These mechanisms need to be mapped onto the neurodevelopment step(s) gone awry that may be associated with cause in autism. Molecular mechanisms include: (i) regulation of gene expression; (ii) pre-mRNA splicing; (iii) protein localization, translation, and turnover; (iv) synaptic transmission; (v) cell signaling; (vi) the functions of cytoskeletal and scaffolding proteins; and (vii) the function of neuronal cell adhesion molecules. While the molecular mechanisms appear broad, they may converge on only one of a few steps during neurodevelopment that perturbs the structure, function, and/or plasticity of neuronal circuitry. While there are many genetic mutations involved, novel treatments may need to target only one of few developmental mechanisms.

Neuroprotective Effects of Ellagic Acid in Alzheimer's Disease: Focus on Underlying Molecular Mechanisms of Therapeutic Potential

2020 ◽  
Vol 26 ◽  
Author(s):  
Nimra Javaid ◽  
Muhammad Ajmal Shah ◽  
Azhar Rasul ◽  
Zunera Chauhdary ◽  
Uzma Saleem ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ellagic Acid ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Acetylcholinesterase Activity ◽  
Neuroprotective Effects

: Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead towards neuronal cell death. Alzheimer’s disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset yet later on it worsens. The documented evidence of AD neuropathology manifested the neuro-inflammation, increased reactive oxygen, nitrogen species and decreased antioxidant protective process; mitochondrial dysfunction as well as increased level of acetylcholinesterase activity. Moreover, enhanced action of proteins leads towards neural apoptosis which have a vital role in the degeneration of neurons. The inability of commercial therapeutic options to treat AD with targeting single mechanism leads the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid, latest studies expressed that ellagic acid can initiate the numerous cell signaling transmission and decrease the progression of disorders, involved in the degeneration of neurons. The influential property of ellagic acid to protect the neurons in neurodegenerative disorders is due to its antioxidant effect, iron chelating and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mode of action of ellagic acid against neurodegeneration.

Sign in / Sign up

Export Citation Format

Share Document