Abstract
Apoptosis is synonymous to programmed cell death, which occurs in response to a plethora of stimuli and employs a series of highly conserved mediators and pathways. Its ambivalent role in immunology is illustrated by the fact that this process not only serves homeostatic functions but also exerts harmful effects including tissue damage. This is particularly true for neuroinflammatory diseases such as multiple sclerosis (MS), the most frequent neurological disease to afflict adolescents in the western world. Considerable insight into the role of apoptosis in MS has been obtained by using its animal model experimental autoimmune encephalomyelitis (EAE). Experiments using the EAE model have revealed that cell death affects both infiltrating lymphocytes and CNS resident cells, and that it contributes to axonal injury as well as the resolution of inflammation. Furthermore, it was discovered that the molecules involved in inducing and regulating this process are the Fas-FasL system, pro- and anti-apoptotic Bcl-2 family members, ‘initiator’ and ‘effector’ caspases, glucocorticoid hormones and various modulatory proteins. The variety of apoptotic mechanisms in combination with their often opposing effects on the disease course highlights the need for a detailed understanding of apoptosis in this context. In the future, this may pave the way to novel approaches aiming at interfering with the apoptotic process to prevent tissue damage or at intentionally inducing cell death in order to ameliorate the disease by deleting autoreactive lymphocytes.
Keywords: Apoptosis, Bcl-2, Fas, glucocorticoid, caspase, EAE, MS, leukocyte, oligodendrocyte, lymphocytes.
Current Pharmaceutical Design
Title:The Ambivalent Role of Apoptosis in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis
Volume: 18 Issue: 29
Author(s): Holger M. Reichardt and Fred Luhder
Affiliation:
Keywords: Apoptosis, Bcl-2, Fas, glucocorticoid, caspase, EAE, MS, leukocyte, oligodendrocyte, lymphocytes.
Abstract: Apoptosis is synonymous to programmed cell death, which occurs in response to a plethora of stimuli and employs a series of highly conserved mediators and pathways. Its ambivalent role in immunology is illustrated by the fact that this process not only serves homeostatic functions but also exerts harmful effects including tissue damage. This is particularly true for neuroinflammatory diseases such as multiple sclerosis (MS), the most frequent neurological disease to afflict adolescents in the western world. Considerable insight into the role of apoptosis in MS has been obtained by using its animal model experimental autoimmune encephalomyelitis (EAE). Experiments using the EAE model have revealed that cell death affects both infiltrating lymphocytes and CNS resident cells, and that it contributes to axonal injury as well as the resolution of inflammation. Furthermore, it was discovered that the molecules involved in inducing and regulating this process are the Fas-FasL system, pro- and anti-apoptotic Bcl-2 family members, ‘initiator’ and ‘effector’ caspases, glucocorticoid hormones and various modulatory proteins. The variety of apoptotic mechanisms in combination with their often opposing effects on the disease course highlights the need for a detailed understanding of apoptosis in this context. In the future, this may pave the way to novel approaches aiming at interfering with the apoptotic process to prevent tissue damage or at intentionally inducing cell death in order to ameliorate the disease by deleting autoreactive lymphocytes.
Export Options
About this article
Cite this article as:
M. Reichardt Holger and Luhder Fred, The Ambivalent Role of Apoptosis in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis, Current Pharmaceutical Design 2012; 18 (29) . https://dx.doi.org/10.2174/138161212802502224
DOI https://dx.doi.org/10.2174/138161212802502224 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
The role of vitamin D towards immune tolerance in white adipose tissue (WAT)
Endocrine, Metabolic & Immune Disorders - Drug Targets Apoptosis and Autoimmune Disease
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents New Drugs for Immune Targeting
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) A Review on Possible Therapeutic Effect of Nigella sativa and Thymoquinone in Neurodegenerative Diseases
CNS & Neurological Disorders - Drug Targets Beta-Adrenergic Antagonists: Indications and Potential Immunomodulatory Side Effects in the Critically Ill
Current Medicinal Chemistry In Vivo Imaging of the Diseased Nervous System: An Update
Current Pharmaceutical Design Graphical Abstracts
Current Neuropharmacology Curcumin: the Yellow Molecule with Pleiotropic Biological Effects
Letters in Drug Design & Discovery Novel Therapeutic Targets in Neuropsychiatric Disorders: The Neuroepigenome
Current Pharmaceutical Design Kv1.3 Lymphocyte Potassium Channel Inhibition as a Potential Novel Therapeutic Target in Acute Ischemic Stroke
CNS & Neurological Disorders - Drug Targets Co-Enzyme Q10 to Treat Neurological Disorders: Basic Mechanisms, Clinical Outcomes, and Future Research Direction
CNS & Neurological Disorders - Drug Targets Protein-Protein Interaction Inhibition (2P2I): Fewer and Fewer Undruggable Targets
Combinatorial Chemistry & High Throughput Screening The Long and Winding Road to Cancer Treatment: The Trail System
Current Pharmaceutical Design Nanomedicine and its Application in Treatment of Microglia-mediated Neuroinflammation
Current Medicinal Chemistry Multiple Sclerosis, Gut Microbiota and Permeability: Role of Tryptophan Catabolites, Depression and the Driving Down of Local Melatonin
Current Pharmaceutical Design Nuclear Imaging of Inflammation in Neurologic and Psychiatric Disorders
Current Clinical Pharmacology GABAergic Agonists Modulate the Glutamate Release from Frontal Cortex Synaptosomes of Rats with Experimental Autoimmune Encephalomyelitis
Inflammation & Allergy - Drug Targets (Discontinued) Glycolipids as Immune Modulatory Tools
Mini-Reviews in Medicinal Chemistry Future Therapeutic Strategies in Inflammatory Cardiomyopathy: Insights from the Experimental Autoimmune Myocarditis Model
Cardiovascular & Hematological Disorders-Drug Targets Merging Traditional Chinese Medicine with Modern Drug Discovery Technologies to Find Novel Drugs and Functional Foods
Current Drug Discovery Technologies