Raman spectroscopy reveals biochemical differences in plasma derived extracellular vesicles from sporadic Amyotrophic Lateral Sclerosis patients

Morasso, Carlo; Sproviero, Daisy; Mimmi, Maria Chiara; Giannini, Marta; Gagliardi, Stella; Vanna, Renzo; Diamanti, Luca; Bernuzzi, Stefano; Piccotti, F; Truffi, Marta; Pansarasa, Orietta; Corsi, Fabio; Cereda, Cristina

doi:10.1016/j.nano.2020.102249

Cited by 43 publications

(52 citation statements)

References 41 publications

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“…We previously demonstrated significant differences between LEVs and SEVs derived from plasma for dimension, markers, protein loading (see Figure S1a-d) [28][29][30]. Cellular miRNAs can selectively traffic into LEVs and SEVs, so we first identified differentially expressed miRNAs (DE miRNAs) in SEVs and LEVs among the four groups of patients (AD, PD, ALS, FTD) and the healthy controls (CTRs) ( Table 1, Table S1).…”

Section: Mirnas Selectively Traffic Into Sevs and Levsmentioning

confidence: 99%

“…However, none of these studies considered the differences between SEVs from LEVs. We previously described in ALS that SEVs and LEVs in plasma are different in dimensions and for loading of some pathological proteins for ALS (SOD1, TDP-43, p-TDP-43, and FUS) and lipids [28][29][30]. In this paper, we have investigated the miRNA cargo of EVs derived from plasma of patients affected by four neurodegenerative diseases (AD, PD, ALS and FTD).…”

Section: Introductionmentioning

confidence: 99%

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

Sproviero

Gagliardi

Zucca

et al. 2021

IJMS

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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.

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Section: Mirnas Selectively Traffic Into Sevs and Levsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Sproviero

Gagliardi

Zucca

et al. 2021

IJMS

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“…We previously demonstrated significant differences between LEVs and SEVs derived from plasma for dimension, markers, protein loading (see figure S1a, b, c, d) [35,40,55]. Cellular miRNAs and RNAs can selectively traffick into LEVs and SEVs, so we first identified differentially expressed miRNAs (DE miRNAs) and mRNAs (DE mRNA) in SEVs and LEVs among the four groups of patients (AD, PD, ALS, FTD) and the healthy controls (CTRs) (Table 3, Table 4, Table S1, Table S2).…”

Section: Resultsmentioning

confidence: 99%

“…We found a variable range of overlap between LEVs and SEVs: for miRNAs in SEVs the percentage was between 18.2-61.5% and in LEVs 25.2-46.2% and for mRNAs 8.4 and 17.1% for SEVs and 35.5 and 34.2 for ALS and FTD patients (Table 5). Although there is some overlap between the two types of EVs, there is a significant difference that may justify, as we already described for dimension, protein and lipid loading [35,40,55], the different functions of LEVs and SEVs in plasma of ND patients. Conley et al characterized protein coding transcripts in SEVs and LEVs from breast cancer patients by RNA-Seq and identified a small fraction of transcripts that were expressed at significantly different levels in large oncosomes and exosomes, suggesting they may mediate specialized functions [56].…”

Section: Discussionmentioning

confidence: 99%

“…However, none of these studies considered the differences between SEVs from LEVs. We previously described in ALS that SEVs and LEVs in plasma are different in dimensions and for loading of some pathological proteins for ALS (SOD1, TDP-43, p-TDP-43, and FUS) and lipids [35,55]. In this paper, we have investigated the RNA cargo of EVs derived from plasma of patients affected by four neurodegenerative diseases (AD, PD, ALS and FTD).…”

Section: Introductionmentioning

confidence: 99%

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

Sproviero

Gagliardi

Zucca

et al. 2020

Preprint

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BackgroundIdentifying 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.

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Nanostructures and Nanotechnologies for the Detection of Extracellular Vesicle

You

Song

et al. 2022

Advanced Biology

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characterization, [1] liquid biopsy analyzes the biomarkers in various body fluids, predominantly the blood, enables minimally invasive, dynamic, and integral molecular analysis of tumors and the detection of minimal residual diseases, provides important information for the early diagnosis, prognostication, and the monitoring of tumor progression and treatment response, and would ultimately facilitate precision medicine and personalized cancer management. Extracellular vesicles (EVs) are emerging liquid biopsies that can provide comprehensive molecular information at the level of DNA, RNA, and protein, allowing for the multicomponent analysis of cancers. The detection and molecular analysis of EVs are challenging due to their small size, and the difficulties to purify them from the multicomponent serum or plasma samples. Nanomaterials, nanostructures, and nanotechnologies have shown their significant advantages in the high-purity isolation and the high-sensitive and high-specific detection of EVs. Nanotechnology-based liquid biopsy holds great potential as companion or surrogate of tissue biopsy in the clinical practice.Currently, some businesses have built a product pipeline and service platforms around their unique ability of using EVs to identify biomarkers for disease surveillance and diagnosis. ExoDx Prostate IntelliScore (EPI) from Exosome Diagnostics (ExosomeDX) [2] has been approved by the US Food and Drug Administration (FDA) for the diagnosis of prostate cancer, and ExoDX Lung (ALK), a biopsy product for the analysis of EVsderived RNA from blood samples, has been approved as a clinical assessment tool for gene mutation-associated nonsmall cell lung cancer (NSCLC). Recently, by deriving differentiated detection parameters, a Nanoparticle EXOsome Sensing (NEXOS) technology was shown to detect sEVs ultrasensitively and multidimensionally, [3] leading to a pilot study of liquid biopsy in liver cancer supported by Roche Diagnostics. Therefore, developing diagnostic strategies based on EV capture, detection, and analysis is of paramount importance to increase the effectiveness of cancer diagnosis.In this review, we focus on the development of nanomaterials, nanostructures, and nanotechniques for the detection and molecular characterization of EVs. The advantages of nanotechnologies in enhancing the capture efficiency, sensitivity, and specificity, and the challenges and opportunities of the nanotechnology-based liquid biopsy for the routine clinical practice are discussed.Liquid biopsy has been taken as a minimally invasive examination and a promising surrogate to the clinically applied tissue-based test for the diagnosis and molecular analysis of cancer. Extracellular vesicles (EVs) carry complex molecular information from the tumor, allowing for the multicomponent analysis of cancer and would be beneficial to personalized medicine. In this review, the advanced nanomaterials and nanotechniques for the detection and molecular profiling of EVs, highlight the advantages of nanotechnology in the high-purity iso...

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Raman spectroscopy reveals biochemical differences in plasma derived extracellular vesicles from sporadic Amyotrophic Lateral Sclerosis patients

Cited by 43 publications

References 41 publications

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

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

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

Nanostructures and Nanotechnologies for the Detection of Extracellular Vesicle

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