Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
Amyotrophic Lateral Sclerosis
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Amyotrophic Lateral Sclerosis

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 (31 December 2020) | Viewed by 29602

Special Issue Editors

Dr. William Camu

E-Mail Website
Guest Editor
Explorations Neurologiques et Centre SLA, Université Montpellier, CHU Gui de Chauliac, INM, INSERM, 34000 Montpellier, France
Interests: amyotrophic lateral sclerosis; clinical trial; epidemiology; environmental factors; biomarkers; genetics; primary lateral sclerosis
Dr. Kevin Mouzat

E-Mail Website
Guest Editor
The Neuroscience Institute of Montpellier, Inserm UMR1051, University of Montpellier, 34091 Montpellier, CHU Nimes, 30029 Nimes, France
Interests: genetics; neurogenetics; amyotrophic lateral sclerosis; functional characterization of variants; molecular biology
Dr. Cédric Raoul

E-Mail Website
Guest Editor
The Institute for Neurosciences of Montpellier Inserm UMR1298, University of Montpellier, 34091 Montpellier, France
Interests: amyotrophic lateral sclerosis; cell death pathway; neuroinflammation; neuroimmunity; electrophysiology; astrocytes; experimental models; gene therapy

Special Issue Information

Dear Colleagues,

Since the first description of the disease in 1869 by Jean-Martin Charcot, our knowledge of many aspects of Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig’s disease) have widely increased. ALS is one of the most severe neurodegenerative diseases, leading to death in a median time of 3 years. It is caused by progressive paralysis of limbs, speech, swallowing and breathing, due to the progressive death of both first and second motoneurons.

This Special Issue of IJMS aims to cover various angles of the disease, from genetic and molecular findings toward clinical perspectives. This Special Issue will also present new insights in the recent efforts of therapeutic developments.

Topics include, not exhaustively, the following:

  • Clinical diagnosis
  • Electrophysiology, imaging, biomarkers
  • Genetics and genomics
  • Pathophysiology
  • Therapeutic developments

Your contribution to this Special Issue, either with original research or review articles, will be highly appreciated.

Prof. Dr. William Camu
Dr. Kevin Mouzat
Dr. Cédric Raoul
Guest Editors

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.

Keywords

  • Amyotrophic lateral sclerosis;
  • Motoneuron;
  • Diagnosis;
  • Patients care;
  • Treatment;
  • Therapy;
  • Genetics;
  • Pathophysiology

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

14 pages, 5619 KiB  
Article
Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation
by Audrey Dangoumau, Sylviane Marouillat, Roxane Coelho, François Wurmser, Céline Brulard, Shanez Haouari, Frédéric Laumonnier, Philippe Corcia, Christian R. Andres, Hélène Blasco and Patrick Vourc’h
Int. J. Mol. Sci. 2021, 22(4), 1796; https://doi.org/10.3390/ijms22041796 - 11 Feb 2021
Cited by 9 | Viewed by 2671
Abstract
Protein aggregates in affected motor neurons are a hallmark of amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to their formation remain incompletely understood. Oxidative stress associated with age, the major risk factor in ALS, contributes to this neurodegeneration in ALS. We [...] Read more.
Protein aggregates in affected motor neurons are a hallmark of amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to their formation remain incompletely understood. Oxidative stress associated with age, the major risk factor in ALS, contributes to this neurodegeneration in ALS. We show that several genes coding for enzymes of the ubiquitin and small ubiquitin-related modifier (SUMO) pathways exhibit altered expression in motor neuronal cells exposed to oxidative stress, such as the CCNF gene mutated in ALS patients. Eleven of these genes were further studied in conditions combining oxidative stress and the expression of an ALS related mutant of the superoxide dismutase 1 (SOD1) gene. We observed a combined effect of these two environmental and genetic factors on the expression of genes, such as Uhrf2, Rbx1, Kdm2b, Ube2d2, Xaf1, and Senp1. Overall, we identified dysregulations in the expression of enzymes of the ubiquitin and SUMO pathways that may be of interest to better understand the pathophysiology of ALS and to protect motor neurons from oxidative stress and genetic alterations. Full article
(This article belongs to the Special Issue Amyotrophic Lateral Sclerosis)
►▼ Show Figures

Figure 1

18 pages, 1560 KiB  
Article
Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis
by Mercedes Lachén-Montes, Naroa Mendizuri, Karina Ausin, Pol Andrés-Benito, Isidro Ferrer, Joaquín Fernández-Irigoyen and Enrique Santamaría
Int. J. Mol. Sci. 2020, 21(21), 8311; https://doi.org/10.3390/ijms21218311 - 5 Nov 2020
Cited by 11 | Viewed by 2538
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive muscle paralysis due to the degeneration of upper and lower motor neurons. Recent studies point out an involvement of the non-motor axis during disease progression. Despite smell impairment being considered a potential [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive muscle paralysis due to the degeneration of upper and lower motor neurons. Recent studies point out an involvement of the non-motor axis during disease progression. Despite smell impairment being considered a potential non-motor finding in ALS, the pathobiochemistry at the olfactory level remains unknown. Here, we applied an olfactory quantitative proteotyping approach to analyze the magnitude of the olfactory bulb (OB) proteostatic imbalance in ALS subjects (n = 12) with respect to controls (n = 8). Around 3% of the quantified OB proteome was differentially expressed, pinpointing aberrant protein expression involved in vesicle-mediated transport, macroautophagy, axon development and gliogenesis in ALS subjects. The overproduction of olfactory marker protein (OMP) points out an imbalance in the olfactory signal transduction in ALS. Accompanying the specific overexpression of glial fibrillary acidic protein (GFAP) and Bcl-xL in the olfactory tract (OT), a tangled disruption of signaling routes was evidenced across the OB–OT axis in ALS. In particular, the OB survival signaling dynamics clearly differ between ALS and frontotemporal lobar degeneration (FTLD), two faces of TDP-43 proteinopathy. To the best of our knowledge, this is the first report on high-throughput molecular characterization of the olfactory proteostasis in ALS. Full article
(This article belongs to the Special Issue Amyotrophic Lateral Sclerosis)
►▼ Show Figures

Figure 1

17 pages, 7873 KiB  
Article
ALS-Related Mutant SOD1 Aggregates Interfere with Mitophagy by Sequestering the Autophagy Receptor Optineurin
by Yeong Jin Tak, Ju-Hwang Park, Hyangshuk Rhim and Seongman Kang
Int. J. Mol. Sci. 2020, 21(20), 7525; https://doi.org/10.3390/ijms21207525 - 13 Oct 2020
Cited by 29 | Viewed by 4652
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive demise of motor neurons. One of the causes of familial ALS is the mutation of the gene encoding superoxide dismutase 1 (SOD1), which leads to abnormal protein aggregates. How SOD1 aggregation [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive demise of motor neurons. One of the causes of familial ALS is the mutation of the gene encoding superoxide dismutase 1 (SOD1), which leads to abnormal protein aggregates. How SOD1 aggregation drives ALS is still poorly understood. Recently, ALS pathogenesis has been functionally implicated in mitophagy, specifically the clearance of damaged mitochondria. Here, to understand this mechanism, we investigated the relationship between the mitophagy receptor optineurin and SOD1 aggregates. We found that mutant SOD1 (mSOD1) proteins associate with and then sequester optineurin, which is required to form the mitophagosomes, to aggregates in N2a cells. Optineurin recruitment into mSOD1 aggregates resulted in a reduced mitophagy flux. Furthermore, we observed that an exogenous augmentation of optineurin alleviated the cellular cytotoxicity induced by mSOD1. Taken together, these studies demonstrate that ALS-linked mutations in SOD1 interfere with the mitophagy process through optineurin sequestration, suggesting that the accumulation of damaged mitochondria may play a crucial role in the pathophysiological mechanisms contributing to ALS. Full article
(This article belongs to the Special Issue Amyotrophic Lateral Sclerosis)
►▼ Show Figures

Figure 1

11 pages, 2032 KiB  
Article
Clinical and Molecular Landscape of ALS Patients with SOD1 Mutations: Novel Pathogenic Variants and Novel Phenotypes. A Single ALS Center Study
by Emilien Bernard, Antoine Pegat, Juliette Svahn, Françoise Bouhour, Pascal Leblanc, Stéphanie Millecamps, Stéphane Thobois, Claire Guissart, Serge Lumbroso and Kevin Mouzat
Int. J. Mol. Sci. 2020, 21(18), 6807; https://doi.org/10.3390/ijms21186807 - 16 Sep 2020
Cited by 26 | Viewed by 3895
Abstract
Mutations in the copper zinc superoxide dismutase 1 (SOD1) gene are the second most frequent cause of familial amyotrophic lateral sclerosis (ALS). Nearly 200 mutations of this gene have been described so far. We report all SOD1 pathogenic variants identified in [...] Read more.
Mutations in the copper zinc superoxide dismutase 1 (SOD1) gene are the second most frequent cause of familial amyotrophic lateral sclerosis (ALS). Nearly 200 mutations of this gene have been described so far. We report all SOD1 pathogenic variants identified in patients followed in the single ALS center of Lyon, France, between 2010 and 2020. Twelve patients from 11 unrelated families are described, including two families with the not yet described H81Y and D126N mutations. Splice site mutations were detected in two families. We discuss implications concerning genetic screening of SOD1 gene in familial and sporadic ALS. Full article
(This article belongs to the Special Issue Amyotrophic Lateral Sclerosis)
►▼ Show Figures

Figure 1

Review

Jump to: Research

18 pages, 1238 KiB  
Review
The Links between ALS and NF-κB
by Emma Källstig, Brian D. McCabe and Bernard L. Schneider
Int. J. Mol. Sci. 2021, 22(8), 3875; https://doi.org/10.3390/ijms22083875 - 8 Apr 2021
Cited by 26 | Viewed by 5286
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease wherein motor neuron degeneration leads to muscle weakness, progressive paralysis, and death within 3–5 years of diagnosis. Currently, the cause of ALS is unknown but, as with several neurodegenerative diseases, the potential role of neuroinflammation [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease wherein motor neuron degeneration leads to muscle weakness, progressive paralysis, and death within 3–5 years of diagnosis. Currently, the cause of ALS is unknown but, as with several neurodegenerative diseases, the potential role of neuroinflammation has become an increasingly popular hypothesis in ALS research. Indeed, upregulation of neuroinflammatory factors have been observed in both ALS patients and animal models. One such factor is the inflammatory inducer NF-κB. Besides its connection to inflammation, NF-κB activity can be linked to several genes associated to familial forms of ALS, and many of the environmental risk factors of the disease stimulate NF-κB activation. Collectively, this has led many to hypothesize that NF-κB proteins may play a role in ALS pathogenesis. In this review, we discuss the genetic and environmental connections between NF-κB and ALS, as well as how this pathway may affect different CNS cell types, and finally how this may lead to motor neuron degeneration. Full article
(This article belongs to the Special Issue Amyotrophic Lateral Sclerosis)
►▼ Show Figures

Figure 1

27 pages, 979 KiB  
Review
Defective Oligodendroglial Lineage and Demyelination in Amyotrophic Lateral Sclerosis
by Elisabeth Traiffort, Séverine Morisset-Lopez, Mireille Moussaed and Amina Zahaf
Int. J. Mol. Sci. 2021, 22(7), 3426; https://doi.org/10.3390/ijms22073426 - 26 Mar 2021
Cited by 11 | Viewed by 3846
Abstract
Motor neurons and their axons reaching the skeletal muscle have long been considered as the best characterized targets of the degenerative process observed in amyotrophic lateral sclerosis (ALS). However, the involvement of glial cells was also more recently reported. Although oligodendrocytes have been [...] Read more.
Motor neurons and their axons reaching the skeletal muscle have long been considered as the best characterized targets of the degenerative process observed in amyotrophic lateral sclerosis (ALS). However, the involvement of glial cells was also more recently reported. Although oligodendrocytes have been underestimated for a longer time than other cells, they are presently considered as critically involved in axonal injury and also conversely constitute a target for the toxic effects of the degenerative neurons. In the present review, we highlight the recent advances regarding oligodendroglial cell involvement in the pathogenesis of ALS. First, we present the oligodendroglial cells, the process of myelination, and the tight relationship between axons and myelin. The histological abnormalities observed in ALS and animal models of the disease are described, including myelin defects and oligodendroglial accumulation of pathological protein aggregates. Then, we present data that establish the existence of dysfunctional and degenerating oligodendroglial cells, the chain of events resulting in oligodendrocyte degeneration, and the most recent molecular mechanisms supporting oligodendrocyte death and dysfunction. Finally, we review the arguments in support of the primary versus secondary involvement of oligodendrocytes in the disease and discuss the therapeutic perspectives related to oligodendrocyte implication in ALS pathogenesis. Full article
(This article belongs to the Special Issue Amyotrophic Lateral Sclerosis)
►▼ Show Figures

Figure 1

61 pages, 4054 KiB  
Review
Amyotrophic Lateral Sclerosis Genes in Drosophila melanogaster
by Sophie Layalle, Laetitia They, Sarah Ourghani, Cédric Raoul and Laurent Soustelle
Int. J. Mol. Sci. 2021, 22(2), 904; https://doi.org/10.3390/ijms22020904 - 18 Jan 2021
Cited by 13 | Viewed by 5696
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disease characterized by the progressive degeneration of upper and lower motoneurons. Most ALS cases are sporadic but approximately 10% of ALS cases are due to inherited mutations in identified genes. ALS-causing mutations were identified [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disease characterized by the progressive degeneration of upper and lower motoneurons. Most ALS cases are sporadic but approximately 10% of ALS cases are due to inherited mutations in identified genes. ALS-causing mutations were identified in over 30 genes with superoxide dismutase-1 (SOD1), chromosome 9 open reading frame 72 (C9orf72), fused in sarcoma (FUS), and TAR DNA-binding protein (TARDBP, encoding TDP-43) being the most frequent. In the last few decades, Drosophila melanogaster emerged as a versatile model for studying neurodegenerative diseases, including ALS. In this review, we describe the different Drosophila ALS models that have been successfully used to decipher the cellular and molecular pathways associated with SOD1, C9orf72, FUS, and TDP-43. The study of the known fruit fly orthologs of these ALS-related genes yielded significant insights into cellular mechanisms and physiological functions. Moreover, genetic screening in tissue-specific gain-of-function mutants that mimic ALS-associated phenotypes identified disease-modifying genes. Here, we propose a comprehensive review on the Drosophila research focused on four ALS-linked genes that has revealed novel pathogenic mechanisms and identified potential therapeutic targets for future therapy. Full article
(This article belongs to the Special Issue Amyotrophic Lateral Sclerosis)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop