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Molecular Research in Multiple Sclerosis

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (25 May 2021) | Viewed by 22140

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Dr. Damiana Pieragostino

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Guest Editor

University of G. d'Annunzio Chieti-Pescara, Chieti, Italy
Interests: proteomics; metabolomics; mass spectrometry; multiple sclerosis; biomarker discovery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating condition of the Central Nervous System (CNS) characterized by a heterogeneous clinical and neuropathological presentation. From this extreme variability depends a diagnostic uncertainty, especially in the early stages of the disease, which increased the interest in finding new disease biomarkers to better understand its etiopathogenetic mechanisms, to make an early diagnosis, to predict prognosis and to help the clinical decision-making. To date the diagnosis is based on clinical sign and symptoms interpretation, coupled with magnetic resonance imaging (MRI) and the detection in cerebrospinal fluid (CSF) of both biomarkers of immunological activation, such as oligoclonal IgG bands, and antibodies against neurotrophic viruses.

The available treatments for MS only slow the the disease course, probably because the etiology and disease mechanisms are poorly understood. Many large-scale studies have conducted for improving knoledges in MS etiopathology and for validating novel biomarkers in MS diagnosis and management even if a better description of MS, its course and the mechanisms underlying its pathogenesis are needed to improve the diagnostic and prognostic path of these patients.

Therefore, I invite authors to submit original experimental works or critical reviews in line with the purpose of this Special Issue, entitled “Multiple Sclerosis ”.

We are looking for novel or established biomarkers in MS coming from the underlying molecular mechanisms that could be used for disease management, from diagnosis to response to therapies. As a Guest Editor, I ensure that each submitted contribution will undergo a careful, rapid, fair and concise review process to minimize publication times. In conclusion, this challenging Special Issue calls on researchers to provide a brighter comprehension of the disease and to establish possible new biomarkes in order to ensure better care of MS patients in the future.

Dr. Damiana Pieragostino
Guest Editor

Keywords

multiple sclerosis
neuroinflammation
molecular biomarker
diagnosis and prognosis
therapeutic targets
multi-omics
molecular mechanisms
omics sciences

Published Papers (6 papers)

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Editorial

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3 pages, 184 KiB

Open AccessEditorial

Molecular Research in Multiple Sclerosis

by Maurine Fucito and Damiana Pieragostino

Int. J. Mol. Sci. 2022, 23(5), 2792; https://doi.org/10.3390/ijms23052792 - 3 Mar 2022

Cited by 1 | Viewed by 1346

Abstract

The Special Issue, “Molecular Research in Multiple Sclerosis”, provides a better comprehension of the disease and establishes possible new biomarkers to ensure better care of MS patients in the future [...] Full article

(This article belongs to the Special Issue Molecular Research in Multiple Sclerosis)

Review

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24 pages, 3808 KiB

Open AccessReview

Contribution of Metabolomics to Multiple Sclerosis Diagnosis, Prognosis and Treatment

by Marianna Gabriella Rispoli, Silvia Valentinuzzi, Giovanna De Luca, Piero Del Boccio, Luca Federici, Maria Di Ioia, Anna Digiovanni, Eleonora Agata Grasso, Valeria Pozzilli, Alessandro Villani, Antonio Maria Chiarelli, Marco Onofrj, Richard G. Wise, Damiana Pieragostino and Valentina Tomassini

Int. J. Mol. Sci. 2021, 22(20), 11112; https://doi.org/10.3390/ijms222011112 - 15 Oct 2021

Cited by 10 | Viewed by 3665

Abstract

Metabolomics-based technologies map in vivo biochemical changes that may be used as early indicators of pathological abnormalities prior to the development of clinical symptoms in neurological conditions. Metabolomics may also reveal biochemical pathways implicated in tissue dysfunction and damage and thus assist in the development of novel targeted therapeutics for neuroinflammation and neurodegeneration. Metabolomics holds promise as a non-invasive, high-throughput and cost-effective tool for early diagnosis, follow-up and monitoring of treatment response in multiple sclerosis (MS), in combination with clinical and imaging measures. In this review, we offer evidence in support of the potential of metabolomics as a biomarker and drug discovery tool in MS. We also use pathway analysis of metabolites that are described as potential biomarkers in the literature of MS biofluids to identify the most promising molecules and upstream regulators, and show novel, still unexplored metabolic pathways, whose investigation may open novel avenues of research. Full article

(This article belongs to the Special Issue Molecular Research in Multiple Sclerosis)

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15 pages, 3541 KiB

Open AccessReview

MicroRNAs, Multiple Sclerosis, and Depression

by Hsiuying Wang

Int. J. Mol. Sci. 2021, 22(15), 7802; https://doi.org/10.3390/ijms22157802 - 21 Jul 2021

Cited by 20 | Viewed by 4023

Abstract

Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects the brain and spinal cord. There are several disease courses in MS including relapsing–remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). Up to 50% of MS patients experience depressive disorders. Major depression (MD) is a serious comorbidity of MS. Many dysfunctions including neuroinflammation, peripheral inflammation, gut dysbiosis, chronic oxidative and nitrosative stress, and neuroendocrine and mitochondrial abnormalities may contribute to the comorbidity between MS and MD. In addition to these actions, medical treatment and microRNA (miRNA) regulation may also be involved in the mechanisms of the comorbidity between MS and MD. In the study, I review many common miRNA biomarkers for both diseases. These common miRNA biomarkers may help further explore the association between MS and MD. Full article

(This article belongs to the Special Issue Molecular Research in Multiple Sclerosis)

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23 pages, 1334 KiB

Open AccessReview

The Impact of SARS-CoV-2 Infection on the Development of Neurodegeneration in Multiple Sclerosis

by Angela Dziedzic, Joanna Saluk-Bijak, Elzbieta Miller, Marcin Niemcewicz and Michal Bijak

Int. J. Mol. Sci. 2021, 22(4), 1804; https://doi.org/10.3390/ijms22041804 - 11 Feb 2021

Cited by 24 | Viewed by 5686

Abstract

The novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global challenge. Currently, there is some information on the consequences of COVID-19 infection in multiple sclerosis (MS) patients, as it is a newly discovered coronavirus, but its far-reaching effects on participation in neurodegenerative diseases seem to be significant. Recent cases reports showed that SARS-CoV-2 may be responsible for initiating the demyelination process in people who previously had no symptoms associated with any nervous system disorders. It is presently known that infection of SARS-CoV-2 evokes cytokine storm syndrome, which may be one of the factors leading to the acute cerebrovascular disease. One of the substantial problems is the coexistence of cerebrovascular disease and MS in an individual’s life span. Epidemiological studies showed an enhanced risk of death rate from vascular disabilities in MS patients of approximately 30%. It has been demonstrated that patients with severe SARS-CoV-2 infection usually show increased levels of D-dimer, fibrinogen, C-reactive protein (CRP), and overactivation of blood platelets, which are essential elements of prothrombotic events. In this review, the latest knowledge gathered during an ongoing pandemic of SARS-CoV-2 infection on the neurodegeneration processes in MS is discussed. Full article

(This article belongs to the Special Issue Molecular Research in Multiple Sclerosis)

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11 pages, 1807 KiB

Open AccessReview

Intrathecal Inflammation in Progressive Multiple Sclerosis

by Salvatore Monaco, Richard Nicholas, Richard Reynolds and Roberta Magliozzi

Int. J. Mol. Sci. 2020, 21(21), 8217; https://doi.org/10.3390/ijms21218217 - 3 Nov 2020

Cited by 34 | Viewed by 3682

Abstract

Progressive forms of multiple sclerosis (MS) are associated with chronic demyelination, axonal loss, neurodegeneration, cortical and deep gray matter damage, and atrophy. These changes are strictly associated with compartmentalized sustained inflammation within the brain parenchyma, the leptomeninges, and the cerebrospinal fluid. In progressive MS, molecular mechanisms underlying active demyelination differ from processes that drive neurodegeneration at cortical and subcortical locations. The widespread pattern of neurodegeneration is consistent with mechanisms associated with the inflammatory molecular load of the cerebrospinal fluid. This is at variance with gray matter demyelination that typically occurs at focal subpial sites, in the proximity of ectopic meningeal lymphoid follicles. Accordingly, it is possible that variations in the extent and location of neurodegeneration may be accounted for by individual differences in CSF flow, and by the composition of soluble inflammatory factors and their clearance. In addition, “double hit” damage may occur at sites allowing a bidirectional exchange between interstitial fluid and CSF, such as the Virchow–Robin spaces and the periventricular ependymal barrier. An important aspect of CSF inflammation and deep gray matter damage in MS involves dysfunction of the blood–cerebrospinal fluid barrier and inflammation in the choroid plexus. Here, we provide a comprehensive review on the role of intrathecal inflammation compartmentalized to CNS and non-neural tissues in progressive MS. Full article

(This article belongs to the Special Issue Molecular Research in Multiple Sclerosis)

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Other

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4 pages, 6124 KiB

Open AccessCase Report

Phelan McDermid Syndrome: Multiple Sclerosis as a Rare but Treatable Cause for Regression—A Case Report

by Sarah Jesse, Jan Philipp Delling, Michael Schön, Tobias M Boeckers, Albert Ludolph and Makbule Senel

Int. J. Mol. Sci. 2021, 22(5), 2311; https://doi.org/10.3390/ijms22052311 - 25 Feb 2021

Cited by 4 | Viewed by 2715

Abstract

Phelan McDermid syndrome (PMcD) is a neurogenetic disease associated with haploinsufficiency of the SHANK3 gene due to a spectrum of anomalies in the terminal region of the long arm of chromosome 22. SHANK3 is the abbreviation for SH3 domain and ankyrin repeat-containing protein, a gene that encodes for proteins of the postsynaptic density (PSD) of excitatory synapses. This PSD is relevant for the induction and plasticity of spine and synapse formation as a basis for learning processes and long-term potentiation. Individuals with PMcD present with intellectual disability, muscular hypotonia, and severely delayed or absent speech. Further neuropsychiatric manifestations cover symptoms of the autism spectrum, epilepsy, bipolar disorders, schizophrenia, and regression. Regression is one of the most feared syndromes by relatives of PMcD patients. Current scientific evidence indicates that the onset of regression is variable and affects language, motor skills, activities of daily living and cognition. In the case of regression, patients normally undergo further diagnostics to exclude treatable reasons such as complex-focal seizures or psychiatric comorbidities. Here, we report, for the first time, the case of a young female who developed progressive symptoms of regression and a dystonic-spastic hemiparesis that could be traced back to a comorbid multiple sclerosis and that improved after treatment with methylprednisolone. Full article

(This article belongs to the Special Issue Molecular Research in Multiple Sclerosis)

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