Pathological Comparison of TDP-43 Between Motor Neurons and Interneurons Expressed by a Tetracycline Repressor System on the Mouse Artificial Chromosome DOI Open Access

Shota Togai,

Shusei Hamamichi, Yasuhiro Kazuki

et al.

Yonago acta medica, Journal Year: 2023, Volume and Issue: 66(1), P. 24 - 35

Published: Jan. 1, 2023

Cytoplasmic mislocalization of TAR-DNA binding protein 43 kDa (TDP-43) is a major hallmark amyotrophic lateral sclerosis (ALS). TDP-43 aggregation detected in the cortical and spinal motor neurons most ALS cases; however, pathological mechanism this mislocalized remains unknown.We generated tetracycline-inducible A315T system on mouse artificial chromosome (MAC) vector to avoid transgene-insertional mutagenesis, established embryonic stem (ES) cell line holding MAC system, investigated whether overexpressed exogenous was cytoplasm ES cell-derived triggered neurotoxic effects these cells.Inducible successfully loaded onto introduced into cells. These cells could differentiate interneurons. Overexpression by addition doxycycline both resulted cytoplasm. Mislocalized caused death neurons, but not interneurons.Vulnerability cytoplasmic selective neuronal types, whereas occurs even insusceptible neurons. This inducible gene expression using useful for providing critical insights appearance pathology.

Language: Английский

Cognition-associated long noncoding RNAs are dysregulated upon severe COVID-19 DOI Creative Commons
Jonathan D. Lee, Isaac H. Solomon, Frank J. Slack

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 12, 2024

Severe COVID-19 leads to widespread transcriptomic changes in the human brain, mimicking diminished cognitive performance. As long noncoding RNAs (lncRNAs) play crucial roles regulation of gene expression, identification lncRNAs differentially expressed upon may nominate key regulatory nodes underpinning changes. Here we identify hundreds brains patients relative uninfected age/sex-matched controls, many which are associated with decreased performance and inflammatory cytokine response. Our analyses reveal pervasive lncRNA expression severe COVID-19, serve as regulators neurocognitive brain.

Language: Английский

Citations

2

Predicting lncRNA–protein interactions through deep learning framework employing multiple features and random forest algorithm DOI Creative Commons
Ying Liang,

XingRui Yin,

YangSen Zhang

et al.

BMC Bioinformatics, Journal Year: 2024, Volume and Issue: 25(1)

Published: March 12, 2024

Abstract RNA-protein interaction (RPI) is crucial to the life processes of diverse organisms. Various researchers have identified RPI through long-term and high-cost biological experiments. Although numerous machine learning deep learning-based methods for predicting currently exist, their robustness generalizability significant room improvement. This study proposes LPI-MFF, an prediction model based on multi-source information fusion, address these issues. The LPI-MFF employed protein–protein interactions features, sequence secondary structure physical chemical properties as sources with corresponding coding scheme, followed by random forest algorithm feature screening. Finally, all was combined a classification method convolutional neural networks used. experimental results fivefold cross-validation demonstrated that accuracy RPI1807 NPInter 97.60% 97.67%, respectively. In addition, rate independent test set RPI1168 84.9%, Mus musculus dataset 90.91%. Accordingly, greater generalization than other prevalent methods.

Language: Английский

Citations

2

The Role of Non-Coding RNAs in Mitochondrial Dysfunction of Alzheimer’s Disease DOI

Samin Abed,

Amir Ebrahimi, Fatemeh Fattahi

et al.

Journal of Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 74(4)

Published: Oct. 28, 2024

Language: Английский

Citations

2

Differentially Expressed Genes and Molecular Susceptibility to Human Age-Related Diseases DOI Open Access

С. Г. Шихевич,

И. В. Чадаева,

Bato Khandaev

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3996 - 3996

Published: Feb. 16, 2023

Mainstream transcriptome profiling of susceptibility versus resistance to age-related diseases (ARDs) is focused on differentially expressed genes (DEGs) specific gender, age, and pathogeneses. This approach fits in well with predictive, preventive, personalized, participatory medicine helps understand how, why, when, what ARDs one can develop depending their genetic background. Within this mainstream paradigm, we wanted find out whether the known ARD-linked DEGs available PubMed reveal a molecular marker that will serve purpose anyone’s any tissue at time. We sequenced periaqueductal gray (PAG) tame aggressive rats, identified rat-behavior-related DEGs, compared them homologous animal DEGs. analysis yielded statistically significant correlations between behavior-related ARD-susceptibility-related fold changes (log2 values) expression these DEG homologs. found principal components, PC1 PC2, corresponding half-sum half-difference log2 values, respectively. With linked ARD humans used as controls, verified components. only common for ARDs: an excess Fcγ receptor IIb suppressing immune cell hyperactivation.

Language: Английский

Citations

5

Long non-coding RNAs with essential roles in neurodegenerative disorders DOI Creative Commons
Wandi Xiong, Linlin Lu, Jiali Li

et al.

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(6), P. 1212 - 1220

Published: Sept. 22, 2023

Abstract Recently, with the advent of high-resolution and high-throughput sequencing technologies, an increasing number long non-coding RNAs (lncRNAs) have been found to be involved in regulation neuronal function central nervous system specific spatiotemporal patterns, across different neurodegenerative diseases. However, underlying mechanisms lncRNAs during neurodegeneration remain poorly understood. This review provides overview current knowledge biology focuses on introducing latest identified roles, regulatory mechanisms, research status Alzheimer’s disease, Parkinson’s Huntington’s amyotrophic lateral sclerosis. Finally, this discusses potential values as diagnostic biomarkers therapeutic targets for diseases, hoping provide broader implications developing effective treatments.

Language: Английский

Citations

3

Long Non-coding RNAs, Extracellular Vesicles and Inflammation in Alzheimer’s Disease DOI Open Access
Ania Canseco-Rodríguez,

Valeria Masola,

Vincenza Aliperti

et al.

Published: Sept. 14, 2022

Alzheimer´s Disease (AD) has currently no effective treatment; however, preventive measures can significantly delay the progress/onset of disease. Thus, accurate and early prediction risk is an important strategy to alleviate AD burden. Neuroinflammation a major factor prompting onset Inflammation exerts its toxic effect via multiple mechanisms. Amongst others, it affecting gene expression modulation non-coding RNAs (ncRNAs), such as miRNAs. Recent evidence supports that inflammation also affect long (lncRNAs) expression. While association between miRNAs in been extensively studied, role lncRNAs neurodegenerative diseases less explored. In this review, we focus on context AD. Furthermore, since plasma-isolated extracellular vesicles (EVs) are increasingly recognized monitoring brain pathologies, have focused studies reporting dysregulated EVs isolated from patients controls. The revised literature shows positive pro-inflammatory However, reports evaluating alterations plasma controls, although still limited confirm value specific associated with reliable biomarkers. This emerging field will open new avenues improve prediction, patients’ stratification may lead discovery potential novel therapeutic targets for

Language: Английский

Citations

5

Advances in endogenous RNA pull-down: A straightforward dextran sulfate-based method enhancing RNA recovery DOI Creative Commons
Fabio Desideri, Eleonora D’Ambra, Pietro Laneve

et al.

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: Oct. 19, 2022

Detecting RNA/RNA interactions in the context of a given cellular system is crucial to gain insights into molecular mechanisms that stand beneath each specific RNA molecule. When it comes non-protein coding (ncRNAs), and especially long noncoding RNAs (lncRNAs), reliability purification dramatically dependent on their abundance. Exogenous methods, which lncRNAs are vitro transcribed incubated with protein extracts or overexpressed by cell transfection, have been extensively used overcome problem However, although useful study contribution single sub-modules RNA/protein interactions, these exogenous practices might fail revealing biologically meaningful contacts occurring vivo risk generate non-physiological artifacts. Therefore, endogenous methods must be preferred, for initial identification partners specifically interacting elected RNAs. Here, we apply an pull-down lncMN2-203, neuron-specific lncRNA contributing robustness motor neurons specification, through interaction miRNA-466i-5p. We show both yield lncMN2-203 recovery specificity its miRNA increase presence Dextran Sulfate Sodium (DSS) salt. This new set-up may represent powerful means improving RNA-RNA biological significance, those whose role as microRNA (miRNA) sponges regulators mRNA stability was demonstrated.

Language: Английский

Citations

5

LncRNA NORAD defects deteriorate the formation of age-related macular degeneration DOI Creative Commons

Jinfeng Zhang,

Jing Jiang, Hongyu Zhou

et al.

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: July 29, 2023

Long noncoding RNAs (lncRNAs) play important roles in the development of age-related macular degeneration (AMD). However, effect long non-coding RNA activated by DNA damage (NORAD) on AMD remains unknown. This study aimed to investigate NORAD RPE cell senescence and degeneration. Irradiated adult retinal pigment epithelial line-19 (ARPE-19) sodium iodate-treated mice were used as vitro vivo models. Results showed that irradiation-induced characteristics ARPE-19 NORAD-knockdown aggravated cycle arrest G2/M phase, apoptosis along with increased expression phosphorylated P53 (p-P53) P21. factors C3, ICAM-1, APP, APOE, VEGF-A also NORAD-knockdown. Moreover, reduction mitochondrial homeostasis factors, (i.e., TFAM POLG) respiratory chain complex genes ND1 ND5) reactive oxygen species (ROS). We identified a strong interaction PGC-1α sirtuin 1 (SIRT1) ARPE-19; is, knockdown increases acetylation PGC-1α. In knockout mice, NORAD-knockout accelerated iodate-reduced thickness reduction, function impairment loss fundus. Therefore, accelerates senescence, apoptosis, markers via acetylation, ROS, p-P53–P21signaling pathway, which NORAD-mediated might occur through direct SIRT1.

Language: Английский

Citations

2

Alzheimer’s disease and microorganisms: the non-coding RNAs crosstalk DOI Creative Commons

Hanieh Mohammadi‐Pilehdarboni,

Mohammad Shenagari,

Farahnaz Joukar

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 5, 2024

Alzheimer’s disease (AD) is a complex, multifactorial disorder, influenced by multitude of variables ranging from genetic factors, age, and head injuries to vascular diseases, infections, various other environmental demographic determinants. Among the role microbiome in genesis neurodegenerative disorders (NDs) gaining increased recognition. This paradigm shift substantiated an extensive body scientific literature, which underscores significant contributions microorganisms, encompassing viruses gut-derived bacteria, pathogenesis AD. The mechanism microbial infection exerts its influence on AD hinges primarily inflammation. Neuroinflammation, activated response acts as defense for brain but can inadvertently lead unexpected neuropathological perturbations, ultimately contributing NDs. Given ongoing uncertainty surrounding factors underpinning ND, comprehensive investigations into particularly viral agents, are imperative. Recent advances neuroscientific research have unveiled pivotal non-coding RNAs (ncRNAs) orchestrating pathways integral pathologies. While upstream regulators governing pathological manifestations microorganisms remain elusive, in-depth exploration nuanced ncRNAs holds promise development prospective therapeutic interventions. review aims elucidate master modulators realm conditions, with specific focus disease.

Language: Английский

Citations

0

Is Diet A Contributing Factor To Infertility? DOI Creative Commons
Ufaque Batool K. Samo,

Kausar Abbas Saldera,

Rizwan Ali Lakho

et al.

ANNALS OF ABBASI SHAHEED HOSPITAL AND KARACHI MEDICAL & DENTAL COLLEGE, Journal Year: 2024, Volume and Issue: 29(1), P. 64 - 70

Published: Feb. 15, 2024

Objective: To evaluate the effect of dietary trans-unsaturated fatty acids (TFAs) on ovulatory infertility in young unmarried females.Methods: This cross-sectional study was conducted from 1 august 2023 to 31 December at Basic Medical Science Institute (BMSI), Jinnah Postgraduate Center Karachi. All healthy females aged 15-25 were included study. Females with a family history infertility, having existing comorbidity, irregular menstruation cycle or hormonal replacement therapy, excluded. Based Food frequency questionnaire score, 300 subjects divided into 3 groups, Group A low trans fats Consumers (Score 0-170), B moderate consumers(Score 171-340) and C high consumers 341-500). The analysis results carried out SPSS Software version 22.Results: study’s respondents, who ranged age 16 25, had mean 21.8 years. Fifteen per cent those group “A” abnormal HDL, 22% bad LDL, 23% TGA, while 17% cholesterol. An 31% participants “B” exhibited cholesterol levels. significant correlation between oxidative stress indicators found three groups: (13%) aberrant LH, “20%” FSH, “11%” serum estrogen, “10%” progesterone, “C” (49% progesterone). (FFQ ) scores 25% positive cholesterol, 40% negative 39% biochemical indicators.Conclusion: Trans diets significantly increase risk reproductive failure

Language: Английский

Citations

0