scholarly journals Different miRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases

2021 ◽  
Vol 22 (5) ◽  
pp. 2737
Author(s):  
Daisy Sproviero ◽  
Stella Gagliardi ◽  
Susanna Zucca ◽  
Maddalena Arigoni ◽  
Marta Giannini ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Extracellular Vesicles ◽  
Small Rnas ◽  
Biomarker Discovery ◽  
Toll Like Receptor ◽  
Neurotrophin Signaling ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Lateral Sclerosis ◽  
Glycosphingolipid Biosynthesis

Identifying biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common and different miRNA signatures in plasma derived LEVs and SEVs of Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia (FTD) patients. LEVs and SEVs were isolated from plasma of patients and healthy volunteers (CTR) by filtration and differential centrifugation and RNA was extracted. Small RNAs libraries were carried out by Next Generation Sequencing (NGS). MiRNAs discriminate all NDs diseases from CTRs and they can provide a signature for each NDs. Common enriched pathways for SEVs were instead linked to ubiquitin mediated proteolysis and Toll-like receptor signaling pathways and for LEVs to neurotrophin signaling and Glycosphingolipid biosynthesis pathway. LEVs and SEVs are involved in different pathways and this might give a specificity to their role in the spreading of the disease. The study of common and different miRNAs transported by LEVs and SEVs can be of great interest for biomarker discovery and for pathogenesis studies in neurodegeneration.

scholarly journals Different RNA profiles in plasma derived small and large extracellular vesicles of Neurodegenerative diseases patients

2020 ◽  
Author(s):  
Daisy Sproviero ◽  
Stella Gagliardi ◽  
Susanna Zucca ◽  
Maddalena Arigoni ◽  
Marta Giannini ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Extracellular Vesicles ◽  
Biomarker Discovery ◽  
Toll Like Receptor ◽  
Neurotrophin Signaling ◽  
Next Generation Sequencing Ngs ◽  
Whole Transcriptome ◽  
Generation Sequencing ◽  
Lateral Sclerosis ◽  
Glycosphingolipid Biosynthesis

AbstractBackgroundIdentifying robust biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common and different mRNA/miRNA signatures in plasma derived LEVs and SEVs of Alzheimer’s Disease (AD), Parkinson’s disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia (FTD) patients.MethodsLEVs and SEVs were isolated from plasma of patients and healthy volunteers (CTR) by filtration and ultracentrifugation and RNA was extracted. Whole transcriptome and miRNA libraries were carried out by Next Generation Sequencing (NGS).ResultsWe detected different deregulated RNAs in LEVs and SEVs from patients with the same disease. MiRNAs resulted to be the most interesting subpopulation of transcripts transported by plasma derived SEVs since they appeared to discriminate all NDs disease from CTRs and they can provide a signature for each NDs. Common enriched pathways for SEVs were mainly linked to ubiquitin mediated proteolysis and Toll-like receptor signaling pathways and for LEVs to neurotrophin signaling and Glycosphingolipid biosynthesis pathway.ConclusionLEVs and SEVs are involved in different pathways and this might give a specificity to their role in the spreading/protection of the disease. The study of common and different RNAs transported by LEVs and SEVs can be of great interest for biomarker discovery and for pathogenesis studies in neurodegeneration.

scholarly journals MicroRNA Profiling of HL-1 Cardiac Cells-Derived Extracellular Vesicles

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 273
Author(s):  
Serena Silvestro ◽  
Agnese Gugliandolo ◽  
Luigi Chiricosta ◽  
Francesca Diomede ◽  
Oriana Trubiani ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Target Genes ◽  
Cell Types ◽  
Cardiac Cells ◽  
Myoblast Differentiation ◽  
Cardiovascular Development ◽  
Adult Cardiomyocytes ◽  
A Cell ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

HL-1 is a cell line that shows a phenotype similar to adult cardiomyocytes. All major cardiac cell types release extracellular vesicles (EVs) that emerge as key mediators of intercellular communication. EVs can mediate intercellular cross-talk through the transfer of specific microRNAs (miRNAs). MiRNAs are known to play important regulatory roles during tissue differentiation and regeneration processes. Furthermore, miRNAs have recently been shown to be involved in the proliferation of adult cardiomyocytes. In this context, the purpose of this study was to analyze the transcriptomic profile of miRNAs expressed from HL-1 cardiac muscle cell-derived EVs, using next generation sequencing (NGS). Specifically, our transcriptomic analysis showed that the EVs derived from our HL-1 cells contained miRNAs that induce blood vessel formation and increase cell proliferation. Indeed, our bioinformatics analysis revealed 26 miRNAs expressed in EVs derived from our HL-1 that target genes related to cardiovascular development. In particular, their targets are enriched for the following biological processes related to cardiovascular development: heart morphogenesis, positive regulation of angiogenesis, artery development, ventricular septum development, cardiac atrium development, and myoblast differentiation. Consequently, EVs could become important in the field of regenerative medicine.

scholarly journals Pathogenic and protective roles of extracellular vesicles in neurodegenerative diseases

2020 ◽  
Author(s):  
Toshihide TAKEUCHI
Keyword(s):  
Neurodegenerative Diseases ◽  
Extracellular Vesicles ◽  
Protein Accumulation ◽  
Progressive Degeneration ◽  
Disease Diagnostics ◽  
Abnormal Accumulation ◽  
Aggregation Formation ◽  
Associated Proteins ◽  
Brain And Spinal Cord ◽  
Lateral Sclerosis

Abstract Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and polyglutamine diseases are caused by aggregation and abnormal accumulation of the disease-causative proteins in brain and spinal cord. Recent studies have suggested that proteins associated with neurodegenerative diseases are secreted and transmitted intercellularly via extracellular vesicles (EVs), which may be involved in propagation of abnormal protein accumulation and progressive degeneration in patient brains. On the other hand, it has been also reported that EVs have neuroprotective roles in these diseases, which potentially contribute to preventing aggregation formation and aberrant accumulation of the disease-associated proteins. In this review, I summarize the current understanding of the roles of EVs in neurodegenerative diseases, especially focussing on the pathogenic and neuroprotective aspects. Elucidation of these two aspects of EVs would provide insight into not only potential therapeutic targets for treatment of neurodegenerative diseases but also development of EV-based biomarkers for disease diagnostics

scholarly journals sRNAanno --- a database repository of uniformly-annotated small RNAs in plants

2019 ◽  
Author(s):  
Chengjie Chen ◽  
Junting Feng ◽  
Bo Liu ◽  
Jiawei Li ◽  
Lei Feng ◽  
...  
Keyword(s):  
Small Rnas ◽  
Genetic Research ◽  
Free Access ◽  
Plant Mirnas ◽  
Integrative Genomics ◽  
Small Interfering Rnas ◽  
Genomic Information ◽  
Free Service ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

AbstractSmall RNAs (sRNAs) are essential regulatory molecules, including three mayor classes in plants, microRNAs (miRNAs), phased small interfering RNAs (phased siRNAs or phasiRNAs), and heterochromatic siRNAs (hc-siRNAs). Except miRNAs, the other two classes are not well-annotated and collected in public databases for most sequenced plant genomes. We performed comprehensive sRNA annotation for 138 plant species, which have fully sequenced genomes and public next-generation-sequencing (NGS) sRNA data available. The results are available via an online repository called sRNAanno (www.plantsRNAs.org). Compared to plant miRNAs deposited in miRBase, we obtained much more miRNAs, which are more complete and reliable because of consistent and high-stringent criteria used in our miRNA annotation. sRNAanno also provides free access to genomic information for >16,000 PHAS loci and >21,000,000 hc-siRNA loci annotated from these 138 plants. On the basis of Integrative Genomics Viewer (IGV), we developed a visualization tool for browsing NGS sRNA data (IGV-sRNA), which have been integrated a series of new functions compatible to specific sRNA features. To make sRNA annotation an easy task, sRNAanno also provides free service of sRNA annotation to the community. In summary, sRNAanno and IGV-sRNA are great resources to facilitate the genomic and genetic research of plant small RNAs.

scholarly journals Extracellular vesicles – propagators of neuropathology and sources of potential biomarkers and therapeutics for neurodegenerative diseases

2020 ◽  
Vol 133 (23) ◽  
pp. jcs243139
Author(s):  
Natasha Vassileff ◽  
Lesley Cheng ◽  
Andrew F. Hill
Keyword(s):  
Neurodegenerative Diseases ◽  
Extracellular Vesicles ◽  
Protein Misfolding ◽  
Therapeutic Potential ◽  
Prion Diseases ◽  
Cellular Communication ◽  
Compensatory Process ◽  
Potential Therapeutics ◽  
Lateral Sclerosis ◽  
Potential Biomarkers

ABSTRACTNeurodegenerative diseases are characterised by the irreversible degeneration of neurons in the central or peripheral nervous systems. These include amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD) and prion diseases. Small extracellular vesicles (sEVs), a type of EV involved in cellular communication, have been well documented as propagating neurodegenerative diseases. These sEVs carry cargo, such as proteins and RNA, to recipient cells but are also capable of promoting protein misfolding, thus actively contributing to the progression of these diseases. sEV secretion is also a compensatory process for lysosomal dysfunction in the affected cells, despite inadvertently propagating disease to recipient cells. Despite this, sEV miRNAs have biomarker potential for the early diagnosis of these diseases, while stem cell-derived sEVs and those generated through exogenous assistance demonstrate the greatest therapeutic potential. This Review will highlight novel advancements in the involvement of sEVs as propagators of neuropathology, biomarkers and potential therapeutics in neurodegenerative diseases.

scholarly journals Individual Oligogenic Background in p.D91A-SOD1 Amyotrophic Lateral Sclerosis Patients

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1843
Author(s):  
Giulia Gentile ◽  
Benedetta Perrone ◽  
Giovanna Morello ◽  
Isabella Laura Simone ◽  
Sebastiano Andò ◽  
...  
Keyword(s):  
Disease Diagnosis ◽  
Untranslated Regions ◽  
Slow Progression ◽  
Uncertain Significance ◽  
Progression Of Disease ◽  
Small Cohort ◽  
Next Generation Sequencing Ngs ◽  
Als Patients ◽  
Generation Sequencing ◽  
Lateral Sclerosis

The p.D91A is one of the most common ALS-causing SOD1 mutations and is known to be either recessive or dominant. The homozygous phenotype is characterized by prolonged survival and slow progression of disease, whereas the affected heterozygous phenotypes can vary. To date, no genetic protective factors located close to SOD1 have been associated with the mild progressive homozygous phenotype. Using Next Generation Sequencing (NGS), we characterized a small cohort of sporadic and familial p.D91A-SOD1 heterozygous (n = 2) or homozygous (n = 5) ALS patients, to reveal any additional contributing variant in 39 ALS-related genes. We detected unique sets of non-synonymous variants, four of which were of uncertain significance and several in untranslated regions of ALS-related genes. Our results supported an individual oligogenic background underlying both sporadic and familial p.D91A cases irrespective of their p.D91A mutant alleles. We suggest that a comprehensive genomic view of p.D91A-SOD1 ALS patients may be useful in identifying emerging variants and improving disease diagnosis as well as guiding precision medicine.

scholarly journals Modulation of Small RNA Signatures in Schwann-Cell-Derived Extracellular Vesicles by the p75 Neurotrophin Receptor and Sortilin

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 450
Author(s):  
Nádia P. Gonçalves ◽  
Yan Yan ◽  
Maj Ulrichsen ◽  
Morten T. Venø ◽  
Ebbe T. Poulsen ◽  
...  
Keyword(s):  
Nerve Regeneration ◽  
Extracellular Vesicles ◽  
Small Rnas ◽  
Axon Growth ◽  
Cell Types ◽  
Neurotrophin Receptor ◽  
Regulatory Function ◽  
P75 Neurotrophin Receptor ◽  
Global Expression Profile ◽  
Neurotrophin Signaling

Schwann cells (SCs) are the main glial cells of the peripheral nervous system (PNS) and are known to be involved in various pathophysiological processes, such as diabetic neuropathy and nerve regeneration, through neurotrophin signaling. Such glial trophic support to axons, as well as neuronal survival/death signaling, has previously been linked to the p75 neurotrophin receptor (p75NTR) and its co-receptor Sortilin. Recently, SC-derived extracellular vesicles (EVs) were shown to be important for axon growth and nerve regeneration, but cargo of these glial cell-derived EVs has not yet been well-characterized. In this study, we aimed to characterize signatures of small RNAs in EVs derived from wild-type (WT) SCs and define differentially expressed small RNAs in EVs derived from SCs with genetic deletions of p75NTR (Ngfr−/−) or Sortilin (Sort1−/−). Using RNA sequencing, we identified a total of 366 miRNAs in EVs derived from WT SCs of which the most highly expressed are linked to the regulation of axonogenesis, axon guidance and axon extension, suggesting an involvement of SC EVs in axonal homeostasis. Signaling of SC EVs to non-neuronal cells was also suggested by the presence of several miRNAs important for regulation of the endothelial cell apoptotic process. Ablated p75NTR or sortilin expression in SCs translated into a set of differentially regulated tRNAs and miRNAs, with impact in autophagy and several cellular signaling pathways such as the phosphatidylinositol signaling system. With this work, we identified the global expression profile of small RNAs present in SC-derived EVs and provided evidence for a regulatory function of these vesicles on the homeostasis of other cell types of the PNS. Differentially identified miRNAs can pave the way to a better understanding of p75NTR and sortilin roles regarding PNS homeostasis and disease.

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