Long Non-Coding RNAs, Novel Offenders or Guardians in Multiple Sclerosis: A Scoping Review

Multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system, is one of the most common neurodegenerative diseases worldwide. MS results in serious neurological dysfunctions and disability. Disturbances in coding and non-coding genes are key components leading to neurodegeneration along with environmental factors. Long non-coding RNAs (lncRNAs) are long molecules in cells that take part in the regulation of gene expression. Several studies have confirmed the role of lncRNAs in neurodegenerative diseases such as MS. In the current study, we performed a systematic analysis of the role of lncRNAs in this disorder. In total, 53 studies were recognized as eligible for this systematic review. Of the listed lncRNAs, 52 lncRNAs were upregulated, 37 lncRNAs were downregulated, and 11 lncRNAs had no significant expression difference in MS patients compared with controls. We also summarized some of the mechanisms of lncRNA functions in MS. The emerging role of lncRNAs in neurodegenerative diseases suggests that their dysregulation could trigger neuronal death via still unexplored RNA-based regulatory mechanisms. Evaluation of their diagnostic significance and therapeutic potential could help in the design of novel treatments for MS.

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Adipokines as Immune Cell Modulators in Multiple Sclerosis

International Journal of Molecular Sciences ◽

10.3390/ijms221910845 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10845

Author(s):

Merel Rijnsburger ◽

Niek Djuric ◽

Inge A. Mulder ◽

Helga E. de Vries

Keyword(s):

Multiple Sclerosis ◽

Immune Cells ◽

Immune Cell ◽

Demyelinating Disease ◽

Therapeutic Potential ◽

Inflammatory Factors ◽

Low Grade ◽

The Central Nervous System ◽

Genetic And Environmental Factors

Multiple sclerosis (MS), a chronic inflammatory and demyelinating disease of the central nervous system (CNS), is a major clinical and societal problem, which has a tremendous impact on the life of patients and their proxies. Current immunomodulatory and anti-inflammatory therapies prove to be relatively effective; however, they fail to concomitantly stop ongoing neurological deterioration and do not reverse acquired disability. The proportion to which genetic and environmental factors contribute to the etiology of MS is still incompletely understood; however, a recent association between MS etiology and obesity was shown, with obesity greatly increasing the risk of developing MS. An altered balance of adipokines, which are white adipose tissue (WAT) hormones, plays an important role in the low-grade chronic inflammation during obesity by their pervasive modification of local and systemic inflammation. Vice versa, inflammatory factors secreted by immune cells affect adipokine function. To explore the role of adipokines in MS pathology, we will here review the reciprocal effects of adipokines and immune cells and summarize alterations in adipokine levels in MS patient cohorts. Finally, we will discuss proof-of-concept studies demonstrating the therapeutic potential of adipokines to target both neuroinflammation and neurodegeneration processes in MS.

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Involvement of Heme Oxygenase-1 in Neuropsychiatric and Neurodegenerative Diseases

Current Pharmaceutical Design ◽

10.2174/1381612824666180717160623 ◽

2018 ◽

Vol 24 (20) ◽

pp. 2283-2302 ◽

Cited By ~ 9

Author(s):

Vivian B. Neis ◽

Priscila B. Rosa ◽

Morgana Moretti ◽

Ana Lucia S. Rodrigues

Keyword(s):

Neurodegenerative Diseases ◽

Heme Oxygenase ◽

Therapeutic Potential ◽

Redox Homeostasis ◽

Antioxidant Defenses ◽

Heme Oxygenase 1 ◽

Physiological Conditions ◽

And Oxidative Stress ◽

Defensive Mechanism

Heme oxygenase (HO) family catalyzes the conversion of heme into free iron, carbon monoxide and biliverdin. It possesses two well-characterized isoforms: HO-1 and HO-2. Under brain physiological conditions, the expression of HO-2 is constitutive, abundant and ubiquitous, whereas HO-1 mRNA and protein are restricted to small populations of neurons and neuroglia. HO-1 is an inducible enzyme that has been shown to participate as an essential defensive mechanism for neurons exposed to oxidant challenges, being related to antioxidant defenses in certain neuropathological conditions. Considering that neurodegenerative diseases (Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Multiple Sclerosis (MS)) and neuropsychiatric disorders (depression, anxiety, Bipolar Disorder (BD) and schizophrenia) are associated with increased inflammatory markers, impaired redox homeostasis and oxidative stress, conditions that may be associated with alterations in HO-levels/activity, the purpose of this review is to present evidence on the possible role of HO-1 in these Central Nervous System (CNS) diseases. In addition, the possible therapeutic potential of targeting brain HO-1 is explored in this review.

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The Role of microRNAs in the Viral Infections

Current Pharmaceutical Design ◽

10.2174/1381612825666190110161034 ◽

2019 ◽

Vol 24 (39) ◽

pp. 4659-4667 ◽

Cited By ~ 4

Author(s):

Mona Fani ◽

Milad Zandi ◽

Majid Rezayi ◽

Nastaran Khodadad ◽

Hadis Langari ◽

...

Keyword(s):

Viral Infections ◽

Rna Viruses ◽

Regulation Of Gene Expression ◽

Molecular Structures ◽

Main Function ◽

Cellular Functions ◽

Viral Genes ◽

Non Coding Rnas ◽

Post Transcriptional Regulation

MicroRNAs (miRNAs) are non-coding RNAs with 19 to 24 nucleotides which are evolutionally conserved. MicroRNAs play a regulatory role in many cellular functions such as immune mechanisms, apoptosis, and tumorigenesis. The main function of miRNAs is the post-transcriptional regulation of gene expression via mRNA degradation or inhibition of translation. In fact, many of them act as an oncogene or tumor suppressor. These molecular structures participate in many physiological and pathological processes of the cell. The virus can also produce them for developing its pathogenic processes. It was initially thought that viruses without nuclear replication cycle such as Poxviridae and RNA viruses can not code miRNA, but recently, it has been proven that RNA viruses can also produce miRNA. The aim of this articles is to describe viral miRNAs biogenesis and their effects on cellular and viral genes.

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The Role of miR-210 in the Biological System: A Current Overview

Human Heredity ◽

10.1159/000509280 ◽

2019 ◽

Vol 84 (6) ◽

pp. 233-239

Author(s):

Xu Hui ◽

Hisham Al-Ward ◽

Fahmi Shaher ◽

Chun-Yang Liu ◽

Ning Liu

Keyword(s):

Gene Expression ◽

Regulation Of Gene Expression ◽

Low Oxygen ◽

Cellular Functions ◽

Regulate Gene Expression ◽

System A ◽

Non Coding Rnas ◽

Post Transcriptional Regulation ◽

A Current

Background: MicroRNAs (miRNAs) represent a group of non-coding RNAs measuring 19–23 nucleotides in length and are recognized as powerful molecules that regulate gene expression in eukaryotic cells. miRNAs stimulate the post-transcriptional regulation of gene expression via direct or indirect mechanisms. Summary: miR-210 is highly upregulated in cells under hypoxia, thereby revealing its significance to cell endurance. Induction of this mRNA expression is an important feature of the cellular low-oxygen response and the most consistent and vigorous target of HIF. Key Message: miR-210 is involved in many cellular functions under the effect of HIF-1α, including the cell cycle, DNA repair, immunity and inflammation, angiogenesis, metabolism, and macrophage regulation. It also plays an important regulatory role in T-cell differentiation and stimulation.

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Myelin oligodendrocyte glycoprotein antibodies in pathologically proven multiple sclerosis: frequency, stability and clinicopathologic correlations

Multiple Sclerosis Journal ◽

10.1177/1352458506072189 ◽

2007 ◽

Vol 13 (1) ◽

pp. 7-16 ◽

Cited By ~ 29

Author(s):

S J Pittock ◽

M Reindl ◽

S Achenbach ◽

T Berger ◽

W Bruck ◽

...

Keyword(s):

Multiple Sclerosis ◽

Western Blot ◽

Demyelinating Disease ◽

Clinical Course ◽

Myelin Oligodendrocyte Glycoprotein ◽

Poor Agreement ◽

Predictive Role ◽

Mog Antibodies ◽

Serial Measurements

Controversy exists regarding the pathogenic or predictive role of anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in patients with multiple sclerosis (MS). Four immunopathological patterns (IP) have been recognized in early active MS lesions, suggesting heterogeneous pathogenic mechanisms. Whether MOG antibodies contribute to this pathological heterogeneity and potentially serve as biomarkers to identify specific pathological patterns is unknown. Here we report the frequencies of antibodies to human recombinant MOG (identified by Western blot and enzymelinked immunoabsorbent assay (ELISA)) in patients with pathologically proven demyelinating disease, and investigate whether antibody status is associated with clinical course, HLA-DR2 genotype, IP or treatment response to plasmapheresis. The biopsy cohort consisted of 72 patients: 12 pattern I, 43 pattern II and 17 pattern III. No association was found between MOG antibody status and conversion to clinically definite MS, DR-2 status, IP or response to plasmapheresis. There was poor agreement between Western blot and ELISA (kappa=0.07 for MOG IgM). Fluctuations in antibody seropositivity were seen for 3/4 patients tested serially by Western blot. This study does not support a pathologic pattern-specific role for MOG-antibodies. Variable MOG-antibody status on serial measurements, coupled with the lack of Western blot and ELISA correlations, raises concern regarding the use of MOG-antibody as an MS biomarker and underscores the need for methodological consensus.

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Therapeutic Potential of AAV1-Rheb(S16H) Transduction against Neurodegenerative Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22063064 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3064

Author(s):

Youngpyo Nam ◽

Gyeong Joon Moon ◽

Sang Ryong Kim

Keyword(s):

Neurodegenerative Diseases ◽

Neurodegenerative Disorders ◽

Therapeutic Potential ◽

Neuroprotective Effect ◽

Active Form ◽

Mammalian Target Of Rapamycin ◽

Regulatory System ◽

Neuronal Population ◽

Vital Role

Neurotrophic factors (NTFs) are essential for cell growth, survival, synaptic plasticity, and maintenance of specific neuronal population in the central nervous system. Multiple studies have demonstrated that alterations in the levels and activities of NTFs are related to the pathology and symptoms of neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease. Hence, the key molecule that can regulate the expression of NTFs is an important target for gene therapy coupling adeno-associated virus vector (AAV) gene. We have previously reported that the Ras homolog protein enriched in brain (Rheb)–mammalian target of rapamycin complex 1 (mTORC1) axis plays a vital role in preventing neuronal death in the brain of AD and PD patients. AAV transduction using a constitutively active form of Rheb exerts a neuroprotective effect through the upregulation of NTFs, thereby promoting the neurotrophic interaction between astrocytes and neurons in AD conditions. These findings suggest the role of Rheb as an important regulator of the regulatory system of NTFs to treat neurodegenerative diseases. In this review, we present an overview of the role of Rheb in neurodegenerative diseases and summarize the therapeutic potential of AAV serotype 1 (AAV1)-Rheb(S16H) transduction in the treatment of neurodegenerative disorders, focusing on diseases, such as AD and PD.

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Multiple sclerosis attacks are associated with picornavirus infections

Multiple Sclerosis Journal ◽

10.1191/1352458504ms1005oa ◽

2004 ◽

Vol 10 (2) ◽

pp. 145-148 ◽

Cited By ~ 21

Author(s):

John D Kriesel ◽

Andrea White ◽

Frederick G Hayden ◽

S L Spruance ◽

Jack Petajan

Keyword(s):

Multiple Sclerosis ◽

At Risk ◽

Demyelinating Disease ◽

Respiratory Infections ◽

Risk Period ◽

Relapsing Remitting ◽

The Central Nervous System ◽

Upper Respiratory ◽

Polymerase Chain

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system, which often follows a relapsing-remitting (RR) course with discrete attacks. MS attacks have been associated with upper respiratory infections (URIs), but the specific viruses responsible have not been identified. We studied a cohort of 16 RRMS patients experiencing URI and followed them for clinically identifiable attacks. The viral causes of 21 separate URIs were investigated using culture and polymerase chain reactio n (PCR) of nasal swab specimens, and by serology. Sibley’s ‘at-risk’ period for MS attacks, beginning two weeks before and continuing for five weeks after a URI, was used for the analysis. Seven of the nine (78%) URIs due to picornaviruses were associated with an MS attack during the at-risk period. By contrast, only two of 12 (17%) picornavirus-negative URIs were associated with an MS attack (P =0.01). The possible role of picornaviruses in the patho genesis of MS deserves further study.

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Is There a Case for a Virus Aetiology in Multiple Sclerosis?

Scottish Medical Journal ◽

10.1177/003693309504000207 ◽

1995 ◽

Vol 40 (2) ◽

pp. 55-62 ◽

Cited By ~ 4

Author(s):

Bernard E. Souberbielle ◽

Paul W.S. Szawlowski ◽

William C. Russell

Keyword(s):

Multiple Sclerosis ◽

Demyelinating Disease ◽

Autoimmune Response ◽

Aggressive Approach ◽

Shetland Islands ◽

North East ◽

High Prevalence ◽

Specific Virus ◽

Very High

Multiple Sclerosis (MS) is a devastating demyelinating disease with a very high prevalence in North-East Scotland and in the Orkney and Shetland Islands. MS appears to be a multifactorial disorder with environmental and genetic elements and it has been proposed that these, in tandem, provoke an autoimmune response giving rise to the disease. Although there is no direct evidence of a specific virus being involved in MS, there are nevertheless grounds for suspecting a viral association. This review discusses these aspects of MS and suggests that a more aggressive approach to unravelling the role of viruses is needed.

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Therapeutic potential and biological role of endogenous antioxidant enzymes in multiple sclerosis pathology

Brain Research Reviews ◽

10.1016/j.brainresrev.2007.07.005 ◽

2007 ◽

Vol 56 (2) ◽

pp. 322-330 ◽

Cited By ~ 107

Author(s):

Gerty Schreibelt ◽

Jack van Horssen ◽

Saskia van Rossum ◽

Christine D. Dijkstra ◽

Benjamin Drukarch ◽

...

Keyword(s):

Multiple Sclerosis ◽

Antioxidant Enzymes ◽

Therapeutic Potential ◽

Biological Role ◽

Endogenous Antioxidant

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A Review of Vascular Disease Risk Factors and Multiple Sclerosis

US Neurology ◽

10.17925/usn.2017.13.02.90 ◽

2017 ◽

Vol 13 (02) ◽

pp. 90

Author(s):

Meena R Kannan ◽

Vijayshree Yadav ◽

◽

Keyword(s):

Risk Factors ◽

Multiple Sclerosis ◽

Vascular Disease ◽

Type Ii Diabetes ◽

Demyelinating Disease ◽

Disease Risk ◽

Current Knowledge ◽

Type Ii Diabetes Mellitus ◽

The Central Nervous System

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system and the most common non-traumatic cause of disability in young adults. Recent research shows that vascular disease risk factors (VDRFs) such as obesity, smoking, hyperlipidemia, hypertension, type II diabetes mellitus, and metabolic syndrome, can influence MS on its onset, disease activity, progression, and resultant disability. This review evaluates the current knowledge on the role of VDRFs on outcomes among people with MS (PwMS) and shows that while VDRF prevalence may or may not be higher among PwMS compared with the general population, its presence can influence MS in myriad ways. Management of VDRFs through early detection and treatment may be a promising approach to improving outcomes in PwMS.

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