Journal Browser

► Journal Browser

Special Issue Information

Dear Colleagues,

The term of silent progression has recently been coined to depict the slow clinical deterioration which, despite an apparent lack of disease activity, insidiously develops in patients with relapsing remitting multiple sclerosis (RRMS). Such a key finding clearly urges us to challenge our current views on MS pathophysiology. This Special Issue is framed by the general idea that, on a common ground of myelin-directed autoimmunity, three combining factors are greatly impacting the clinical outcome of multiple sclerosis: age, gender, and the spinal cord localization of MS lesions. The main goal of this issue is thus to gather relevant data and/or analyses which explore one or several of the following points:

a) the molecular impact of gender and/or aging on MS pathophysiology or its animal model;

b) the molecular effects of sex hormones and/or aging on glial cells and/or immune cells;

c) the spinal cord-specific molecular signature of glial cells under normal or pathological conditions.

Prof. Dr. Serge Nataf
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (3 papers)

Download All Papers

Editorial

Jump to: Research, Other

3 pages, 165 KiB

Open AccessEditorial

Cord–Age–Gender Connections Shape the Pathophysiology of Multiple Sclerosis Progressive Forms

by Serge Nataf

Int. J. Mol. Sci. 2019, 20(20), 5103; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20205103 - 15 Oct 2019

Cited by 2 | Viewed by 2067

Abstract

There is increasing evidence that sex hormones, aging, and the occurrence of spinal cord (SC) tissue alterations exert combined effects on the development and outcome of multiple sclerosis (MS) progressive forms [...] Full article

(This article belongs to the Special Issue The Cord-Age-Gender Connection in Multiple Sclerosis Pathophysiology)

Research

Jump to: Editorial, Other

19 pages, 1493 KiB

Open AccessArticle

TGFB1-Mediated Gliosis in Multiple Sclerosis Spinal Cords Is Favored by the Regionalized Expression of HOXA5 and the Age-Dependent Decline in Androgen Receptor Ligands

by Serge Nataf, Marine Guillen and Laurent Pays

Int. J. Mol. Sci. 2019, 20(23), 5934; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20235934 - 26 Nov 2019

Cited by 16 | Viewed by 4469

Abstract

In multiple sclerosis (MS) patients with a progressive form of the disease, spinal cord (SC) functions slowly deteriorate beyond age 40. We previously showed that in the SC of these patients, large areas of incomplete demyelination extend distance away from plaque borders and are characterized by a unique progliotic TGFB1 (Transforming Growth Factor Beta 1) genomic signature. Here, we attempted to determine whether region- and age-specific physiological parameters could promote the progression of SC periplaques in MS patients beyond age 40. An analysis of transcriptomics databases showed that, under physiological conditions, a set of 10 homeobox (HOX) genes are highly significantly overexpressed in the human SC as compared to distinct brain regions. Among these HOX genes, a survey of the human proteome showed that only HOXA5 encodes a protein which interacts with a member of the TGF-beta signaling pathway, namely SMAD1 (SMAD family member 1). Moreover, HOXA5 was previously found to promote the TGF-beta pathway. Interestingly, SMAD1 is also a protein partner of the androgen receptor (AR) and an unsupervised analysis of gene ontology terms indicates that the AR pathway antagonizes the TGF-beta/SMAD pathway. Retrieval of promoter analysis data further confirmed that AR negatively regulates the transcription of several members of the TGF-beta/SMAD pathway. On this basis, we propose that in progressive MS patients, the physiological SC overexpression of HOXA5 combined with the age-dependent decline in AR ligands may favor the slow progression of TGFB1-mediated gliosis. Potential therapeutic implications are discussed. Full article

(This article belongs to the Special Issue The Cord-Age-Gender Connection in Multiple Sclerosis Pathophysiology)

► Show Figures

Graphical abstract

Other

Jump to: Editorial, Research

5 pages, 543 KiB

Open AccessCommentary

The Demonstration of an Aqp4/Tgf-Beta 1 Pathway in Murine Astrocytes Holds Implications for Both Neuromyelitis Optica and Progressive Multiple Sclerosis

by Serge Nataf

Int. J. Mol. Sci. 2020, 21(3), 1035; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21031035 - 04 Feb 2020

Cited by 7 | Viewed by 2797

Abstract

The role exerted by Aquaporin 4 (AQP4) as a regulator of astrocyte immune functions has been poorly explored. A recent report demonstrates that under neuroinflammatory conditions, the expression of Aqp4 on murine astrocytes is mandatory for the effective control of acute inflammation in the central nervous system. Such an immunomodulatory function appears to be mediated by a promotion of the transforming growth factor beta 1 (Tgfb1) pathway. Here, these results are discussed in the context of neuromyelitis optica (NMO) and multiple sclerosis (MS) progressive forms. It is proposed that NMO and progressive MS might rely on opposite molecular mechanisms involving, in NMO, an acutely-defective AQP4/TGFB1 pathway and, in progressive MS, a chronically-stimulated AQP4/TGFB1 pathway. Data supporting the involvement of angiotensin II as a molecular link between AQP4 and TGFB1 are also reviewed. Full article

(This article belongs to the Special Issue The Cord-Age-Gender Connection in Multiple Sclerosis Pathophysiology)

► Show Figures