Abstract
Given the lack of effective drug treatments for amyotrophic lateral sclerosis (ALS), compelling preclinical data on stem cell research has targeted this disease as a candidate for stem cell treatment. Stem cell transplantation has been effective in several animal models, but the underlying biological pathways of restorative processes are still unresolved. Several mechanisms such as cell fusion, neurotrophic factor release, endogenous stem cell proliferation, and transdifferentiation may explain positive therapeutic results in preclinical animal models, in addition to replacement of lost motor neurons. The clinical target in ALS has shifted from being neuroncentered to focus on the interaction between motor neurons and non-neuronal cells (mainly astroglial or microglial). In fact, one of the fundamental unanswered questions in ALS is whether and how much motor neuron death depends on neighboring cells, and how wildtype non-neuronal cells may protect motor neurons expressing an ALS-causing mutation. Lately, motor neuron replacement has been successfully achieved in animal models with reinnervation of the muscle target. Even if many biological issues need to be solved in preclinical models, preliminary stem cell transplantation trials have been performed in ALS patients with conflicting results. The review discusses relevant topics regarding the application of stem cell research to ALS focusing on their therapeutic relevance and mechanisms of action.
Keywords: Amyotrophic lateral sclerosis, motor neuron, stem cells, transplantation, protection, replacement
CNS & Neurological Disorders - Drug Targets
Title: Stem Cells in Amyotrophic Lateral Sclerosis: Motor Neuron Protection or Replacement?
Volume: 9 Issue: 3
Author(s): V. Silani, C. Calzarossa, L. Cova and N. Ticozzi
Affiliation:
Keywords: Amyotrophic lateral sclerosis, motor neuron, stem cells, transplantation, protection, replacement
Abstract: Given the lack of effective drug treatments for amyotrophic lateral sclerosis (ALS), compelling preclinical data on stem cell research has targeted this disease as a candidate for stem cell treatment. Stem cell transplantation has been effective in several animal models, but the underlying biological pathways of restorative processes are still unresolved. Several mechanisms such as cell fusion, neurotrophic factor release, endogenous stem cell proliferation, and transdifferentiation may explain positive therapeutic results in preclinical animal models, in addition to replacement of lost motor neurons. The clinical target in ALS has shifted from being neuroncentered to focus on the interaction between motor neurons and non-neuronal cells (mainly astroglial or microglial). In fact, one of the fundamental unanswered questions in ALS is whether and how much motor neuron death depends on neighboring cells, and how wildtype non-neuronal cells may protect motor neurons expressing an ALS-causing mutation. Lately, motor neuron replacement has been successfully achieved in animal models with reinnervation of the muscle target. Even if many biological issues need to be solved in preclinical models, preliminary stem cell transplantation trials have been performed in ALS patients with conflicting results. The review discusses relevant topics regarding the application of stem cell research to ALS focusing on their therapeutic relevance and mechanisms of action.
Export Options
About this article
Cite this article as:
Silani V., Calzarossa C., Cova L. and Ticozzi N., Stem Cells in Amyotrophic Lateral Sclerosis: Motor Neuron Protection or Replacement?, CNS & Neurological Disorders - Drug Targets 2010; 9 (3) . https://dx.doi.org/10.2174/187152710791292666
DOI https://dx.doi.org/10.2174/187152710791292666 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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 Variable Presentations of Glycogen Storage Disease Type IV: A Review of Clinical, Enzymatic and Molecular Studies
Current Molecular Medicine Advanced Techniques for Imaging the Human Spinal Cord: Review of Literature
Current Medical Imaging Pathogenic Mechanisms and Therapeutic Strategies in Spinobulbar Muscular Atrophy
CNS & Neurological Disorders - Drug Targets A Translational View of Peptide Treatment of Neurological Disorders
Current Medicinal Chemistry Reversal of Bone Cancer Pain by HSV-1-Mediated Silencing of CNTF in an Afferent Area of the Spinal Cord Associated with AKT-ERK Signal Inhibition
Current Gene Therapy Cellular Redox Modulator, ortho Mn(III) meso-tetrakis(N-n-Hexylpyridinium-2-yl)porphyrin, MnTnHex-2-PyP5+ in the Treatment of Brain Tumors
Anti-Cancer Agents in Medicinal Chemistry Sweet and Sour - Oxidative and Carbonyl Stress in Neurological Disorders
CNS & Neurological Disorders - Drug Targets Editorial (Thematic Issue: An Overwiew on the Chemistry and Biochemistry of Triterpenoids)
Mini-Reviews in Organic Chemistry Rho-kinase (ROCK) Inhibitors - A Neuroprotective Therapeutic Paradigm with a Focus on Ocular Utility
Current Medicinal Chemistry Potential Therapeutic Targets for Neurodegenerative Diseases: Lessons Learned from Calorie Restriction
Current Drug Targets Mesenchymal Stem Cells in the Treatment of Amyotrophic Lateral Sclerosis
Current Stem Cell Research & Therapy Is the Cytoskeleton an Intracellular Receptor for Adrenomedullin and PAMP?
Current Protein & Peptide Science Transcriptomics Study of Neurodegenerative Disease: Emphasis on Synaptic Dysfunction Mechanism in Alzheimer's Disease
CNS & Neurological Disorders - Drug Targets State Dissociation, Human Behavior, and Consciousness
Current Topics in Medicinal Chemistry Progranulin Regulates Inflammation and Tumor
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Principles and Therapeutic Relevance for Targeting Mitochondria in Aging and Neurodegenerative Diseases
Current Pharmaceutical Design Biochemical, Molecular and Epigenetic Mechanisms of Valproic Acid Neuroprotection
Current Molecular Pharmacology Inhibitors of Protein-Protein Interactions as Potential Drugs
Current Computer-Aided Drug Design Towards Environmental Construct Validity in Animal Models of CNS Disorders: Optimizing Translation of Preclinical Studies
CNS & Neurological Disorders - Drug Targets Etiology of Neuroinflammatory Pathologies in Neurodegenerative Diseases: A Treatise
Current Psychopharmacology