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Molecular Research of Amyotrophic Lateral Sclerosis
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Molecular Research of Amyotrophic Lateral Sclerosis

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 (30 June 2024) | Viewed by 12933

Special Issue Editor

Dr. Elisabetta Pupillo

E-Mail Website
Guest Editor
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Lombardia, Italy
Interests: ALS

Special Issue Information

Dear Colleagues,

To date, more than 130 treatments have been tested in amyotrophic lateral sclerosis, but no agents with substantial efficacy on disease progression have been found. New information about epidemiological and genetical factors has been explored in recent years, moving our research activity towards new therapeutic strategies.

The present Special Issue aims to explore, but is not limited to, the following topics:

  • An overview of the current research on the promising molecular and cellular mechanisms of therapeutic agents in ALS;
  • Identification of new agents/combination of agents on ALS in preclinical or clinical studies;
  • Systematic review on molecular insight in ALS;
  • Methodological issues and challenges in the treatment of ALS (related both to disease progression or symptoms management);
  • Overview of animal studies performed in ALS: issues, strength, pros and cons.

Dr. Elisabetta Pupillo
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.

Keywords

  • amyotrophic lateral sclerosis
  • ALS
  • motor neuron
  • therapeutic strategies

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Published Papers (4 papers)

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Research

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19 pages, 507 KiB  
Article
Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis
by Anca Moțățăianu, Ion Bogdan Mănescu, Georgiana Șerban, Laura Bărcuțean, Valentin Ion, Rodica Bălașa and Sebastian Andone
Int. J. Mol. Sci. 2024, 25(10), 5059; https://doi.org/10.3390/ijms25105059 - 7 May 2024
Viewed by 1778
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of motor neurons. Emerging evidence suggests a potential link between metabolic dysregulation and ALS pathogenesis. This study aimed to investigate the relationship between metabolic hormones and disease progression in ALS [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of motor neurons. Emerging evidence suggests a potential link between metabolic dysregulation and ALS pathogenesis. This study aimed to investigate the relationship between metabolic hormones and disease progression in ALS patients. A cross-sectional study was conducted involving 44 ALS patients recruited from a tertiary care center. Serum levels of insulin, total amylin, C-peptide, active ghrelin, GIP (gastric inhibitory peptide), GLP-1 active (glucagon-like peptide-1), glucagon, PYY (peptide YY), PP (pancreatic polypeptide), leptin, interleukin-6, MCP-1 (monocyte chemoattractant protein-1), and TNFα (tumor necrosis factor alpha) were measured, and correlations with ALSFRS-R, evolution scores, and biomarkers were analyzed using Spearman correlation coefficients. Subgroup analyses based on ALS subtypes, progression pattern of disease, and disease progression rate patterns were performed. Significant correlations were observed between metabolic hormones and ALS evolution scores. Insulin and amylin exhibited strong correlations with disease progression and clinical functional outcomes, with insulin showing particularly robust associations. Other hormones such as C-peptide, leptin, and GLP-1 also showed correlations with ALS progression and functional status. Subgroup analyses revealed differences in hormone levels based on sex and disease evolution patterns, with male patients showing higher amylin and glucagon levels. ALS patients with slower disease progression exhibited elevated levels of amylin and insulin. Our findings suggest a potential role for metabolic hormones in modulating ALS progression and functional outcomes. Further research is needed to elucidate the underlying mechanisms and explore the therapeutic implications of targeting metabolic pathways in ALS management. Full article
(This article belongs to the Special Issue Molecular Research of Amyotrophic Lateral Sclerosis)
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Review

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21 pages, 607 KiB  
Review
Understanding Amyotrophic Lateral Sclerosis: Pathophysiology, Diagnosis, and Therapeutic Advances
by Radu Eugen Rizea, Antonio-Daniel Corlatescu, Horia Petre Costin, Adrian Dumitru and Alexandru Vlad Ciurea
Int. J. Mol. Sci. 2024, 25(18), 9966; https://doi.org/10.3390/ijms25189966 - 15 Sep 2024
Viewed by 4007
Abstract
This review offers an in-depth examination of amyotrophic lateral sclerosis (ALS), addressing its epidemiology, pathophysiology, clinical presentation, diagnostic techniques, and current as well as emerging treatments. The purpose is to condense key findings and illustrate the complexity of ALS, which is shaped by [...] Read more.
This review offers an in-depth examination of amyotrophic lateral sclerosis (ALS), addressing its epidemiology, pathophysiology, clinical presentation, diagnostic techniques, and current as well as emerging treatments. The purpose is to condense key findings and illustrate the complexity of ALS, which is shaped by both genetic and environmental influences. We reviewed the literature to discuss recent advancements in understanding molecular mechanisms such as protein misfolding, mitochondrial dysfunction, oxidative stress, and axonal transport defects, which are critical for identifying potential therapeutic targets. Significant progress has been made in refining diagnostic criteria and identifying biomarkers, leading to earlier and more precise diagnoses. Although current drug treatments provide some benefits, there is a clear need for more effective therapies. Emerging treatments, such as gene therapy and stem cell therapy, show potential in modifying disease progression and improving the quality of life for ALS patients. The review emphasizes the importance of continued research to address challenges such as disease variability and the limited effectiveness of existing treatments. Future research should concentrate on further exploring the molecular foundations of ALS and developing new therapeutic approaches. The implications for clinical practice include ensuring the accessibility of new treatments and that healthcare systems are equipped to support ongoing research and patient care. Full article
(This article belongs to the Special Issue Molecular Research of Amyotrophic Lateral Sclerosis)
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26 pages, 724 KiB  
Review
Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS
by Aven Lee, Robert Henderson, James Aylward and Pamela McCombe
Int. J. Mol. Sci. 2024, 25(3), 1871; https://doi.org/10.3390/ijms25031871 - 3 Feb 2024
Viewed by 1809
Abstract
Many pathogenetic mechanisms have been proposed for amyotrophic lateral sclerosis (ALS). Recently, there have been emerging suggestions of a possible role for the gut microbiota. Gut microbiota have a range of functions and could influence ALS by several mechanisms. Here, we review the [...] Read more.
Many pathogenetic mechanisms have been proposed for amyotrophic lateral sclerosis (ALS). Recently, there have been emerging suggestions of a possible role for the gut microbiota. Gut microbiota have a range of functions and could influence ALS by several mechanisms. Here, we review the possible role of gut-derived neurotoxins/excitotoxins. We review the evidence of gut symptoms and gut dysbiosis in ALS. We then examine a possible role for gut-derived toxins by reviewing the evidence that these molecules are toxic to the central nervous system, evidence of their association with ALS, the existence of biochemical pathways by which these molecules could be produced by the gut microbiota and existence of mechanisms of transport from the gut to the blood and brain. We then present evidence that there are increased levels of these toxins in the blood of some ALS patients. We review the effects of therapies that attempt to alter the gut microbiota or ameliorate the biochemical effects of gut toxins. It is possible that gut dysbiosis contributes to elevated levels of toxins and that these could potentially contribute to ALS pathogenesis, but more work is required. Full article
(This article belongs to the Special Issue Molecular Research of Amyotrophic Lateral Sclerosis)
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20 pages, 695 KiB  
Review
The Role of Short-Chain Fatty Acids in Microbiota–Gut–Brain Cross-Talk with a Focus on Amyotrophic Lateral Sclerosis: A Systematic Review
by Anca Moțățăianu, Georgiana Șerban and Sebastian Andone
Int. J. Mol. Sci. 2023, 24(20), 15094; https://doi.org/10.3390/ijms242015094 - 11 Oct 2023
Cited by 11 | Viewed by 4810
Abstract
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by the gradual loss of motor neurons in the brain and spinal cord, leading to progressive motor function decline. Unfortunately, there is no effective treatment, and its increasing prevalence is linked to an aging [...] Read more.
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by the gradual loss of motor neurons in the brain and spinal cord, leading to progressive motor function decline. Unfortunately, there is no effective treatment, and its increasing prevalence is linked to an aging population, improved diagnostics, heightened awareness, and changing lifestyles. In the gastrointestinal system, the gut microbiota plays a vital role in producing metabolites, neurotransmitters, and immune molecules. Short-chain fatty acids, of interest for their potential health benefits, are influenced by a fiber- and plant-based diet, promoting a diverse and balanced gut microbiome. These fatty acids impact the body by binding to receptors on enteroendocrine cells, influencing hormones like glucagon-like peptide-1 and peptide YY, which regulate appetite and insulin sensitivity. Furthermore, these fatty acids impact the blood–brain barrier, neurotransmitter levels, and neurotrophic factors, and directly stimulate vagal afferent nerves, affecting gut–brain communication. The vagus nerve is a crucial link between the gut and the brain, transmitting signals related to appetite, inflammation, and various processes. Dysregulation of this pathway can contribute to conditions like obesity and irritable bowel syndrome. Emerging evidence suggests the complex interplay among these fatty acids, the gut microbiota, and environmental factors influences neurodegenerative processes via interconnected pathways, including immune function, anti-inflammation, gut barrier, and energy metabolism. Embracing a balanced, fiber-rich diet may foster a diverse gut microbiome, potentially impacting neurodegenerative disease risk. Comprehensive understanding requires further research into interventions targeting the gut microbiome and fatty acid production and their potential therapeutic role in neurodegeneration. Full article
(This article belongs to the Special Issue Molecular Research of Amyotrophic Lateral Sclerosis)
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