Abstract
There is extensive evidence that changes in immune system activation accompany the pathological changes of Alzheimers disease (AD), but a mechanistic understanding of how the immune system actually participates in disease pathogenesis is still largely lacking. Because of the complexity of the immunological response, and the difficulty in identifying the key molecular players that underlie any given immunological response, expanding our understanding of the immunological response in AD beyond its descriptive stages has not been a straightforward exercise. The development of transgenic animals that form deposits of Aβ peptide in their brains has provided an unexpected dividend to those interested in the immunological response characterizing AD. Several of these transgenic models develop structures greatly resembling neuritic plaques, a hallmark feature of AD brain that is also a focal point of the immunological response occurring in AD. Genetic and pharmacological manipulation of these Aβ-depositing transgenic mice is providing some intriguing and unexpected insights into the role of innate and adaptive immune mechanisms in the pathogenesis of AD. This review will discuss immunological perspectives that have arisen from research using Aβ-depositing transgenic mice, and place these perspectives in the context of epidemiological and genetic studies that have previously suggested a role for the immune system in AD. The emerging story affirms the likely role of innate and adaptive immune mechanisms in the pathogenesis of AD, but provides a cautionary note as to the difficulties that are likely to face potential immunomodulatory therapies due to the dualistic beneficial and detrimental roles that immune mechanisms appear to play in AD.
Keywords: mhc-class II positive microglia, aging, nsaids, inflammatory response, amyloid angiopathy, immunomodulator
Current Pharmaceutical Design
Title: The Dualistic Nature of Immune Modulation In Alzheimers Disease: Lessons from the Transgenic Models
Volume: 11 Issue: 26
Author(s): R. B. Nelson
Affiliation:
Keywords: mhc-class II positive microglia, aging, nsaids, inflammatory response, amyloid angiopathy, immunomodulator
Abstract: There is extensive evidence that changes in immune system activation accompany the pathological changes of Alzheimers disease (AD), but a mechanistic understanding of how the immune system actually participates in disease pathogenesis is still largely lacking. Because of the complexity of the immunological response, and the difficulty in identifying the key molecular players that underlie any given immunological response, expanding our understanding of the immunological response in AD beyond its descriptive stages has not been a straightforward exercise. The development of transgenic animals that form deposits of Aβ peptide in their brains has provided an unexpected dividend to those interested in the immunological response characterizing AD. Several of these transgenic models develop structures greatly resembling neuritic plaques, a hallmark feature of AD brain that is also a focal point of the immunological response occurring in AD. Genetic and pharmacological manipulation of these Aβ-depositing transgenic mice is providing some intriguing and unexpected insights into the role of innate and adaptive immune mechanisms in the pathogenesis of AD. This review will discuss immunological perspectives that have arisen from research using Aβ-depositing transgenic mice, and place these perspectives in the context of epidemiological and genetic studies that have previously suggested a role for the immune system in AD. The emerging story affirms the likely role of innate and adaptive immune mechanisms in the pathogenesis of AD, but provides a cautionary note as to the difficulties that are likely to face potential immunomodulatory therapies due to the dualistic beneficial and detrimental roles that immune mechanisms appear to play in AD.
Export Options
About this article
Cite this article as:
Nelson B. R., The Dualistic Nature of Immune Modulation In Alzheimers Disease: Lessons from the Transgenic Models, Current Pharmaceutical Design 2005; 11 (26) . https://dx.doi.org/10.2174/138161205774370843
DOI https://dx.doi.org/10.2174/138161205774370843 |
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
-
Subject Index To Volume 2
Current Nutrition & Food Science Types of Voltage-Gated Calcium Channels: Molecular and Electrophysiological Views
Current Hypertension Reviews NGF and BDNF Alterations by Prenatal Alcohol Exposure
Current Neuropharmacology The Role of Cellular Senescence During Vascular Calcification: A Key Paradigm in Aging Research
Current Aging Science Defining Primary and Secondary Progenitor Disorders in the Brain: Proteomic Approaches for Analysis of Neural Progenitor Cells
Current Pharmaceutical Biotechnology Adamantane – A Lead Structure for Drugs in Clinical Practice
Current Medicinal Chemistry Editorial : (Thematic issue: Critical Appraisal of Ischemic Stroke Pathophysiology: Road to Cerebral Resuscitation? Part II)
Current Medicinal Chemistry Role of CD73 in Disease: Promising Prognostic Indicator and Therapeutic Target
Current Medicinal Chemistry Different Inductive Effects of Praziquantel Racemate and its Enantiomers on the Enzyme CYP3A4 Mediated by Pregnane X Receptor and its Variants
Current Drug Metabolism Functional Foods: Salient Features and Clinical Applications
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Pharmacology of Appetite Suppression: Implication for the Treatment of Obesity
Current Drug Targets Biological Characteristics and Role of Histamine in Case of Allergic Rhinitis
Medicinal Chemistry Reviews - Online (Discontinued) Commentary [Targeting Opioid Receptors: A New Treatment for Brain Disorders]
CNS & Neurological Disorders - Drug Targets Stem Cell Therapy: A Promising Approach in Treatment of COVID-19
Current Stem Cell Research & Therapy Hematopoietic Transplants for Disease Suppression and Cure in Type 1 Diabetes
Current Stem Cell Research & Therapy Alcohol Use and Cataract
Current Drug Abuse Reviews Current Acetylcholinesterase-Inhibitors: A Neuroinformatics Perspective
CNS & Neurological Disorders - Drug Targets Characterization of Heme Oxygenase in Adult Rodent Platelets
Current Neurovascular Research Phosphodiesterase Inhibitors as a Target for Cognition Enhancement in Aging and Alzheimer’s Disease: A Translational Overview
Current Pharmaceutical Design Pharmacotherapy for Bipolar Depression: A Review of the Evidence
Current Psychiatry Reviews