Abstract
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons which brings to muscular atrophy, paralysis and death in 3-5 years from starting symptoms. In about 10% of cases ALS is familiar and in a relevant percent of these cases, mutations of the enzyme copper-zinc superoxide dismutase 1 (SOD1) are found. Transgenic mice expressing mutated forms of SOD1 replicate with fidelity the onset and progression of the disease and have been largely used to test therapies to be translated to patients in clinical trials. Over years, many therapeutic approaches have been attempted in mice model often with significant, albeit limited, benefits on disease onset, progression and lifespan. Unfortunately almost all the clinical trials based on these preclinical results, have been unsuccessful. In the present review, both results of preclinical and clinical studies are summarized, focusing on the main mechanisms that are believed to contribute to this complex disease: oxidative stress, excitotoxicity, neuroinflammation, mitochondrial dysfunction, errors in protein folding and disposal, lack of trophic factors. Future perspectives related to genetic and stem cell approaches are briefly considered.
Keywords: Amyotrophic lateral sclerosis, clinical trials, animal models, therapy, oxidative stress, excitotoxicity, neuroinflammation, mitochondrial damage, protein aggregates, neurotrophic factors, gene therapy, stem cells
Current Medicinal Chemistry
Title: Amyotrophic Lateral Sclerosis: From Research to Therapeutic Attempts and Therapeutic Perspectives
Volume: 18 Issue: 36
Author(s): A. Contestabile
Affiliation:
Keywords: Amyotrophic lateral sclerosis, clinical trials, animal models, therapy, oxidative stress, excitotoxicity, neuroinflammation, mitochondrial damage, protein aggregates, neurotrophic factors, gene therapy, stem cells
Abstract: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons which brings to muscular atrophy, paralysis and death in 3-5 years from starting symptoms. In about 10% of cases ALS is familiar and in a relevant percent of these cases, mutations of the enzyme copper-zinc superoxide dismutase 1 (SOD1) are found. Transgenic mice expressing mutated forms of SOD1 replicate with fidelity the onset and progression of the disease and have been largely used to test therapies to be translated to patients in clinical trials. Over years, many therapeutic approaches have been attempted in mice model often with significant, albeit limited, benefits on disease onset, progression and lifespan. Unfortunately almost all the clinical trials based on these preclinical results, have been unsuccessful. In the present review, both results of preclinical and clinical studies are summarized, focusing on the main mechanisms that are believed to contribute to this complex disease: oxidative stress, excitotoxicity, neuroinflammation, mitochondrial dysfunction, errors in protein folding and disposal, lack of trophic factors. Future perspectives related to genetic and stem cell approaches are briefly considered.
Export Options
About this article
Cite this article as:
Contestabile A., Amyotrophic Lateral Sclerosis: From Research to Therapeutic Attempts and Therapeutic Perspectives, Current Medicinal Chemistry 2011; 18 (36) . https://dx.doi.org/10.2174/092986711798347289
DOI https://dx.doi.org/10.2174/092986711798347289 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Telomeric Repeat Containing RNA (TERRA): Aging and Cancer
CNS & Neurological Disorders - Drug Targets Directions for Enhancement of the Therapeutic Efficacy of Mesenchymal Stem Cells in Different Neurodegenerative and Cardiovascular Diseases: Current Status and Future Perspectives
Current Stem Cell Research & Therapy The Ubiquitin-Proteasome System and Proteasome Inhibitors in Central Nervous System Diseases
Cardiovascular & Hematological Disorders-Drug Targets HIV-1 Induced CNS Dysfunction: Current Overview and Research Priorities
Current HIV Research Neurorescue Activity, APP Regulation and Amyloid-β Peptide Reduction by Novel Multi-Functional Brain Permeable Iron- Chelating- Antioxidants,M-30 and Green Tea Polyphenol, EGCG
Current Alzheimer Research The Long Non-Coding RNAs in Neurodegenerative Diseases: Novel Mechanisms of Pathogenesis
Current Alzheimer Research Interactions of VDAC with Proteins Involved in Neurodegenerative Aggregation: An Opportunity for Advancement on Therapeutic Molecules
Current Medicinal Chemistry Potential of Antibiotics for the Treatment and Management of Parkinson's Disease: An Overview
Current Drug Research Reviews State of the Art Clinical Efficacy and Safety Evaluation of N-Acetylcarnosine Dipeptide Ophthalmic Prodrug. Principles for the Delivery, Self-Bioactivation, Molecular Targets and Interaction with a Highly Evolved Histidyl-Hydrazide Structure in the Treatment and Therapeutic Management of a Group of Sight-Threatening Eye Diseases
Current Clinical Pharmacology Insights into the Structure, Function, and Regulation of Human Cytochrome P450 1A2
Current Drug Metabolism Genomic and Pharmacogenomic Biomarkers of Parkinson’s Disease
Current Drug Metabolism Editorial [Hot Topic: Mitochondria as a Pharmacological Target: A Clue for Efficacy and a Reason for Toxicity (Executive Guest Editor: Nadezda Apostolova)]
Current Pharmaceutical Design Therapeutic Efficacy of Selegiline in Neurodegenerative Disorders and Neurological Diseases
Current Drug Targets From Bone to Brain: Human Skeletal Stem Cell Therapy for Stroke
Central Nervous System Agents in Medicinal Chemistry Targeting TRPs in Neurodegenerative Disorders
Current Topics in Medicinal Chemistry C. elegans Genetic Networks Predict Roles for O-GlcNAc Cycling in Key Signaling Pathways
Current Signal Transduction Therapy Gene Expression Studies in Multiple Sclerosis
Current Genomics Peptide Therapeutics in Neurodegenerative Disorders
Current Medicinal Chemistry Nanocarriers for Tracking and Treating Diseases
Current Medicinal Chemistry Preparation of Hymenialdisine, Analogues and Their Evaluation as Kinase Inhibitors
Current Medicinal Chemistry