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Molecular Research on Amyotrophic Lateral Sclerosis 2.0
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Molecular Research on Amyotrophic Lateral Sclerosis 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 4877

Special Issue Editors

Dr. Luisa Agnello

E-Mail Website
Guest Editor
University of Palermo, Department of Biomedicine, Neuroscience, and advanced diagnostics, Institute of Clinical Biochemistry and Clinical Laboratory Medicine
Interests: BIoamrkers; laboratory medicine; sepsis; cardiovascular disease; machine learning; neurological diseases; Alzheimer's disease
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Marcello Ciaccio

E-Mail Website
Guest Editor
Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Palermo, Italy
Interests: multiple sclerosis; neurodegeneration; dementia; vitamin D; cerebrospinal fluid biomarkers; molecular and cellular neuroscience
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Amyotrophic lateral sclerosis (ALS) is a rare progressive, lethal, degenerative disease of motor neurons for which there is no treatment currently available. It exists in two forms: sporadic (90% of cases) and familiar due to mutations in more than 20 genes.

The exact pathophysiological mechanism underlying selective motor neuron degeneration is still unclear, but the involvement of some pathways has been hypothesized, including oxidative damage, defects in axonal transport, inflammation, and mitochondrial dysfunction. Additionally, the diagnosis of ALS is challenging and typically takes many months to complete. Thus, there is ongoing research to unravel the cellular mechanisms involved in the development and progression of the disease, explore the role of genetics and other potential risk factors, detect biomarkers, and develop new treatments.

We invite contributions of original research papers, reviews,  as well as position/theoretical papers. Studies combining experimental approaches, including genetic/epigenetic interventions, and cellular, biochemical, molecular, and -omics analyses, are encouraged.

Dr. Luisa Agnello
Prof. Dr. Marcello Ciaccio
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

  • motor neuron
  • ALS
  • neurodegeneration
  • biomarkers
  • treatment
  • genes
  • genetic

Published Papers (2 papers)

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15 pages, 5024 KiB  
Article
Rapid and Robust Multi-Phenotypic Assay System for ALS Using Human iPS Cells with Mutations in Causative Genes
by Tosho Kondo, Ihori Ebinuma, Hirotaka Tanaka, Yukitoshi Nishikawa, Takaki Komiya, Mitsuru Ishikawa and Hideyuki Okano
Int. J. Mol. Sci. 2023, 24(8), 6987; https://doi.org/10.3390/ijms24086987 - 10 Apr 2023
Cited by 2 | Viewed by 2663
Abstract
Amyotrophic lateral sclerosis (ALS) is a major life-threatening disease caused by motor neuron degeneration. More effective treatments through drug discovery are urgently needed. Here, we established an effective high-throughput screening system using induced pluripotent stem cells (iPSCs). Using a Tet-On-dependent transcription factor expression [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a major life-threatening disease caused by motor neuron degeneration. More effective treatments through drug discovery are urgently needed. Here, we established an effective high-throughput screening system using induced pluripotent stem cells (iPSCs). Using a Tet-On-dependent transcription factor expression system carried on the PiggyBac vector, motor neurons were efficiently and rapidly generated from iPSCs by a single-step induction method. Induced iPSC transcripts displayed characteristics similar to those of spinal cord neurons. iPSC-generated motor neurons carried a mutation in fused in sarcoma (FUS) and superoxide dismutase 1 (SOD1) genes and had abnormal protein accumulation corresponding to each mutation. Calcium imaging and multiple electrode array (MEA) recordings demonstrated that ALS neurons were abnormally hyperexcitable. Noticeably, protein accumulation and hyperexcitability were ameliorated by treatment with rapamycin (mTOR inhibitor) and retigabine (Kv7 channel activator), respectively. Furthermore, rapamycin suppressed ALS neuronal death and hyperexcitability, suggesting that protein aggregate clearance through the activation of autophagy effectively normalized activity and improved neuronal survival. Our culture system reproduced several ALS phenotypes, including protein accumulation, hyperexcitability, and neuronal death. This rapid and robust phenotypic screening system will likely facilitate the discovery of novel ALS therapeutics and stratified and personalized medicine for sporadic motor neuron diseases. Full article
(This article belongs to the Special Issue Molecular Research on Amyotrophic Lateral Sclerosis 2.0)
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13 pages, 1232 KiB  
Article
Study of Ubiquitin Pathway Genes in a French Population with Amyotrophic Lateral Sclerosis: Focus on HECW1 Encoding the E3 Ligase NEDL1
by Shanez Haouari, Christian Robert Andres, Debora Lanznaster, Sylviane Marouillat, Céline Brulard, Audrey Dangoumau, Devina Ung, Charlotte Veyrat-Durebex, Frédéric Laumonnier, Hélène Blasco, Philippe Couratier, Philippe Corcia and Patrick Vourc’h
Int. J. Mol. Sci. 2023, 24(2), 1268; https://doi.org/10.3390/ijms24021268 - 09 Jan 2023
Viewed by 1548
Abstract
The ubiquitin pathway, one of the main actors regulating cell signaling processes and cellular protein homeostasis, is directly involved in the pathophysiology of amyotrophic lateral sclerosis (ALS). We first analyzed, by a next-generation sequencing (NGS) strategy, a series of genes of the ubiquitin [...] Read more.
The ubiquitin pathway, one of the main actors regulating cell signaling processes and cellular protein homeostasis, is directly involved in the pathophysiology of amyotrophic lateral sclerosis (ALS). We first analyzed, by a next-generation sequencing (NGS) strategy, a series of genes of the ubiquitin pathway in two cohorts of familial and sporadic ALS patients comprising 176 ALS patients. We identified several pathogenic variants in different genes of this ubiquitin pathway already described in ALS, such as FUS, CCNF and UBQLN2. Other variants of interest were discovered in new genes studied in this disease, in particular in the HECW1 gene. We have shown that the HECT E3 ligase called NEDL1, encoded by the HECW1 gene, is expressed in neurons, mainly in their somas. Its overexpression is associated with increased cell death in vitro and, very interestingly, with the cytoplasmic mislocalization of TDP-43, a major protein involved in ALS. These results give new support for the role of the ubiquitin pathway in ALS, and suggest further studies of the HECW1 gene and its protein NEDL1 in the pathophysiology of ALS. Full article
(This article belongs to the Special Issue Molecular Research on Amyotrophic Lateral Sclerosis 2.0)
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