Abstract
Amyotrophic lateral sclerosis (ALS) is a clinically severe and fatal neurodegenerative disease characterized by a loss of both upper and lower motor neurons, resulting in progressive muscle loss and paralysis. While the exact cause of neuronal death in ALS remains unknown, it is proposed that multiple molecular defects trigger motor neuron cell death. These pathophysiological mechanisms include oxidative stress, mitochondrial impairment, protein aggregation, glutamate cytotoxicity, transcription dysfunction, inflammation, and apoptotic cell death. An understanding of how these potential therapeutic targets interrelate will provide direction both in the development of a pharmacotherapy and in the design of clinical trials in ALS. Important issues related to therapeutic development are the principals that should be followed in designing and conducting experiments using genetic animal models and what body of evidence is desirable to fully inform clinical decision making. In the context of ALS, we review some of the salient issues related to the use of genetic models in providing a guide to assessing studies in translating therapeutic strategies to patients with ALS and discuss therapeutic targets and pharmacological approaches to slowing disease progression. As in other neurodegenerative diseases, the most effective neuroprotection may result from combined treatment strategies.
Keywords: Amyotrophic lateral sclerosis, therapy, neuroprotection, motor neuron, transgenic mice, clinical trials
Mini-Reviews in Medicinal Chemistry
Title: Translational Therapeutic Str ategies in Amyotrophic Lateral Sclerosis
Volume: 7 Issue: 2
Author(s): Hoon Ryu and Robert J. Ferrante
Affiliation:
Keywords: Amyotrophic lateral sclerosis, therapy, neuroprotection, motor neuron, transgenic mice, clinical trials
Abstract: Amyotrophic lateral sclerosis (ALS) is a clinically severe and fatal neurodegenerative disease characterized by a loss of both upper and lower motor neurons, resulting in progressive muscle loss and paralysis. While the exact cause of neuronal death in ALS remains unknown, it is proposed that multiple molecular defects trigger motor neuron cell death. These pathophysiological mechanisms include oxidative stress, mitochondrial impairment, protein aggregation, glutamate cytotoxicity, transcription dysfunction, inflammation, and apoptotic cell death. An understanding of how these potential therapeutic targets interrelate will provide direction both in the development of a pharmacotherapy and in the design of clinical trials in ALS. Important issues related to therapeutic development are the principals that should be followed in designing and conducting experiments using genetic animal models and what body of evidence is desirable to fully inform clinical decision making. In the context of ALS, we review some of the salient issues related to the use of genetic models in providing a guide to assessing studies in translating therapeutic strategies to patients with ALS and discuss therapeutic targets and pharmacological approaches to slowing disease progression. As in other neurodegenerative diseases, the most effective neuroprotection may result from combined treatment strategies.
Export Options
About this article
Cite this article as:
Ryu Hoon and Ferrante J. Robert, Translational Therapeutic Str ategies in Amyotrophic Lateral Sclerosis, Mini-Reviews in Medicinal Chemistry 2007; 7 (2) . https://dx.doi.org/10.2174/138955707779802570
DOI https://dx.doi.org/10.2174/138955707779802570 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...read 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
Related Articles
-
The Potential Role of Glycogen Synthase Kinase 3 Inhibitors as Amyotrophic Lateral Sclerosis Pharmacological Therapy
Current Medicinal Chemistry New Insights into the Roles of Endolysosomal Cathepsins in the Pathogenesis of Alzheimers Disease: Cathepsin Inhibitors as Potential Therapeutics
CNS & Neurological Disorders - Drug Targets Short-Term Ultramicronized Palmitoylethanolamide Therapy in Patients with Myasthenia Gravis: a Pilot Study to Possible Future Implications of Treatment
CNS & Neurological Disorders - Drug Targets Biochemical, Molecular and Epigenetic Mechanisms of Valproic Acid Neuroprotection
Current Molecular Pharmacology Blood-Brain Barrier Transport of Drugs for the Treatment of Brain Diseases
CNS & Neurological Disorders - Drug Targets RNA Therapeutics Directed to the Non Coding Regions of APP mRNA, In Vivo Anti-Amyloid Efficacy of Paroxetine, Erythromycin, and N-acetyl cysteine
Current Alzheimer Research A Multicenter, Double-Blind, Placebo-Controlled Trial of the PDE9A Inhibitor, PF-04447943, in Alzheimer's Disease
Current Alzheimer Research The Urokinase Receptor in the Central Nervous System
CNS & Neurological Disorders - Drug Targets Metal Protein Attenuating Compounds (MPACs): An Emerging Approach for the Treatment of Neurodegenerative Disorders
Current Bioactive Compounds Hypothalamic and Neuroendocrine Changes in Huntingtons Disease
Current Drug Targets Lactoferrin as a Natural Immune Modulator
Current Pharmaceutical Design Oxidative RNA Damage and Neurodegeneration
Current Medicinal Chemistry Therapeutic Approaches to Polyglutamine Diseases: Combating Protein Misfolding and Aggregation
Current Pharmaceutical Design Tauopathies – Focus on Changes at the Neurovascular Unit
Current Alzheimer Research O-Arylation of Iodophenols with 2-Fluorobenzaldehyde Under Microwave Conditions
Letters in Drug Design & Discovery Can Transcriptomics Cut the Gordian Knot of Amyotrophic Lateral Sclerosis?
Current Genomics Inhalational Anesthetic Sevoflurane Rescues Retina Function in Alzheimer’s Disease Transgenic Drosophila
Current Alzheimer Research Therapeutical Potential of CB<sub>2</sub> Receptors in Immune-Related Diseases
Current Molecular Pharmacology Polyphenols and Stem Cells for Neuroregeneration in Parkinson’s Disease and Amyotrophic Lateral Sclerosis
Current Pharmaceutical Design Glutamate Carboxypeptidase II in Diagnosis and Treatment of Neurologic Disorders and Prostate Cancer
Current Medicinal Chemistry