Small nucleolar RNAs in plasma extracellular vesicles and their discriminatory power as diagnostic biomarkers of Alzheimer's disease

Fitz, Nicholas F.; Wang, Jiebiao; Kamboh, M. Ilyas; Koldamova, Radosveta; Lefterov, Iliya

doi:10.1016/j.nbd.2021.105481

Cited by 28 publications

(20 citation statements)

References 78 publications

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“…Lee et al [ 75 ] found that in patients suffering from Post-Traumatic Stress Disorder (PTSD), all patient samples contained EVs with significantly higher proportions ( p < 1 × 10 −4 ) of tRNAs compared to EV depleted plasma and plasma. Fitz et al [ 76 ] investigated the potential of using plasma EV associated RNAs to differentiate between Alzheimer’s disease (AD) patients and normal controls who have no dementia. tRNAs were found to contribute only 4.7% of the genes mapped.…”

Section: Resultsmentioning

confidence: 99%

The Clinical Significance of Transfer RNAs Present in Extracellular Vesicles

Liu

Yang

Asim

et al. 2022

IJMS

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Extracellular vesicles (EVs) are important for intercellular signalling in multi-cellular organisms. However, the role of mature transfer RNAs (tRNAs) and tRNA fragments in EVs has yet to be characterised. This systematic review aimed to identify up-to-date literature on tRNAs present within human EVs and explores their potential clinical significance in health and disease. A comprehensive and systematic literature search was performed, and the study was conducted in accordance with PRISMA guidelines. Electronic databases MEDLINE and EMBASE were searched up until 1 January 2022. From 685 papers, 60 studies were identified for analysis. The majority of papers reviewed focussed on the role of EV tRNAs in cancers (31.7%), with numerous other conditions represented. Blood and cell lines were the most common EV sources, representing 85.9% of protocols used. EV isolation methods included most known methods, precipitation being the most common (49.3%). The proportion of EV tRNAs was highly variable, ranging between 0.04% to >95% depending on tissue source. EV tRNAs are present in a multitude of sources and show promise as disease markers in breast cancer, gastrointestinal cancers, and other diseases. EV tRNA research is an emerging field, with increasing numbers of papers highlighting novel methodologies for tRNA and tRNA fragment discovery.

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Section: Resultsmentioning

confidence: 99%

The Clinical Significance of Transfer RNAs Present in Extracellular Vesicles

Liu

Yang

Asim

et al. 2022

IJMS

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“…The dysregulation of U3 small nucleolar ribonucleoproteins genes (SNORD3B-1, SNORD3A, SNORD3B-2, SNORD3C, and SNORD3D) are related to age-related immune dysfunction (Rahmatpanah et al, 2019 ), G0/G1 to S phase transition (Valleron et al, 2012 ), oxidative-/ER-stress (23349890), and pathogenesis of AD (Fitz et al, 2021 ). These genes are involved in ribosome biosynthesis and early disruption in this pathway is counted as one of the earliest events in the onset of AD (Ding et al, 2005 ).…”

Section: Discussionmentioning

confidence: 99%

Temporal Cortex Microarray Analysis Revealed Impaired Ribosomal Biogenesis and Hyperactivity of the Glutamatergic System: An Early Signature of Asymptomatic Alzheimer's Disease

et al. 2022

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Pathogenic aging is regarded as asymptomatic AD when there is no cognitive deficit except for neuropathology consistent with Alzheimer's disease. These individuals are highly susceptible to developing AD. Braak and Braak's theory specific to tau pathology illustrates that the brain's temporal cortex region is an initiation site for early AD progression. So, the hub gene analysis of this region may reveal early altered biological cascades that may be helpful to alleviate AD in an early stage. Meanwhile, cognitive processing also drags its attention because cognitive impairment is the ultimate result of AD. Therefore, this study aimed to explore changes in gene expression of aged control, asymptomatic AD (AsymAD), and symptomatic AD (symAD) in the temporal cortex region. We used microarray data sets to identify differentially expressed genes (DEGs) with the help of the R programming interface. Further, we constructed the protein-protein interaction (PPI) network by performing the STRING plugin in Cytoscape and determined the hub genes via the CytoHubba plugin. Furthermore, we conducted Gene Ontology (GO) enrichment analysis via Bioconductor's cluster profile package. Resultant, the AsymAD transcriptome revealed the early-stage changes of glutamatergic hyperexcitability. Whereas the connectivity of major hub genes in this network indicates a shift from initially reduced rRNA biosynthesis in the AsymAD group to impaired protein synthesis in the symAD group. Both share the phenomenon of breaking tight junctions and others. In conclusion, this study offers new understandings of the early biological vicissitudes that occur in the brain before the manifestation of symAD and gives new promising therapeutic targets for early AD intervention.

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“…Instead, the snoRNAs, SNORD50B, SNORA3, and U3 have been implicated in animal models of cancer [49][50][51][52]. Additionally, SNORA73 may have a role in ovarian function [53] and EV derived SNORD115 may function as a diagnostic biomarker of Alzheimer's disease [54]. The Ingenuity pathway analysis (IPA) bioinformatics analysis platform had limited information on the identified EV ncRNAs.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Secretome’s Biomarker and Analgesic Potential

Hershfield¹,

Strain²,

Chavez³

et al. 2022

AJPN

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Diagnostic and prognostic biomarkers of nerve injury and/or pain as well as improved pain therapeutics are needed, both on the battlefield to treat injured Service Members and in the civilian sector. Our previous research indicates that there are several differentially expressed (DE) extracellular vesicle-derived microRNAs (EV-miRNAs) isolated from rat plasma following spinal nerve ligation (SNL). As such, EV-miRNAs hold promise as biomarkers and therapeutic targets. The secretome contains biological mediators, including EVs, which are released into the extracellular space. In this study we focus on evaluating EV-non-coding RNAs (ncRNAs), examine effects of SNL on key protein expression in the prefrontal cortex (PFC), and test the secretome's analgesic properties. To accomplish these goals, anesthetized male Sprague Dawley rats underwent SNL and nociceptive behavior measurements, plasma collection followed by EV RNA isolation, small RNA sequencing, and analysis. Expression of several key proteins in the PFC was determined by Wes/Jess analysis. The secretome bath was applied directly to the ligated nerve and the paw withdrawal threshold (PWT) was measured. We identified differences in several classes of ncRNAs such as piRNAs, snoRNAs, and snRNAs post-SNL. Levels of phosphorylated forms of P70S6K and ERK1 were increased in the dorsal PFC at 15 days post-SNL. Bath application of the secretome directly to the ligated nerve resulted in recovery of the reduced PWT (increased mechanical sensitivity) that is induced by SNL. Here, we have identified specific EV-ncRNAs that could contribute to the formation of pain. Furthermore, we have evaluated a novel product for analgesic efficacy that could function to exploit the underlying mechanisms that contribute to pain development, thus reducing acute pain. This is key in treating Service Members on the battlefield in order to prevent pain chronification.

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Small nucleolar RNAs in plasma extracellular vesicles and their discriminatory power as diagnostic biomarkers of Alzheimer's disease

Cited by 28 publications

References 78 publications

The Clinical Significance of Transfer RNAs Present in Extracellular Vesicles

The Clinical Significance of Transfer RNAs Present in Extracellular Vesicles

Temporal Cortex Microarray Analysis Revealed Impaired Ribosomal Biogenesis and Hyperactivity of the Glutamatergic System: An Early Signature of Asymptomatic Alzheimer's Disease

Exploring the Secretome’s Biomarker and Analgesic Potential

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