Abstract
Alzheimer’s disease (AD) is characterized by three major histopathological hallmarks: β-amyloid deposits, neurofibrillary tangles and gliosis. While neglected for decades, the neuroinflammatory processes coordinated by microglia are now accepted as etiologic events in AD evolution. Microglial cells are found in close vicinity to amyloid plaques and display various activation phenotypes determined by the expression of a wide range of cytokines, chemokines, and innate immune surface receptors. During the development of AD pathology, microglia fail to restrict amyloid plaques and may contribute to neurotoxicity and cognitive deficit. Nevertheless, under specific activation states, microglia can participate in cerebral amyloid clearance. This review focuses on the complex relationship between microglia and Aβ pathology, and highlights both deleterious and beneficial roles of microglial activation states in the context of AD. A deeper understanding of microglial biology will hopefully pave the way for next-generation AD therapeutic approaches aimed at harnessing these enigmatic innate immune cells of the central nervous system.
Keywords: Alzheimer disease, amyloid-β peptide, chemokine, cytokine, gliosis, inflammation, innate immunity, microglia, neuroinflammation, phagocytosis.
CNS & Neurological Disorders - Drug Targets
Title:Innate Immunity in Alzheimer’s Disease: A Complex Affair
Volume: 12 Issue: 5
Author(s): Marie-Victoire Guillot-Sestier and Terrence Town
Affiliation:
Keywords: Alzheimer disease, amyloid-β peptide, chemokine, cytokine, gliosis, inflammation, innate immunity, microglia, neuroinflammation, phagocytosis.
Abstract: Alzheimer’s disease (AD) is characterized by three major histopathological hallmarks: β-amyloid deposits, neurofibrillary tangles and gliosis. While neglected for decades, the neuroinflammatory processes coordinated by microglia are now accepted as etiologic events in AD evolution. Microglial cells are found in close vicinity to amyloid plaques and display various activation phenotypes determined by the expression of a wide range of cytokines, chemokines, and innate immune surface receptors. During the development of AD pathology, microglia fail to restrict amyloid plaques and may contribute to neurotoxicity and cognitive deficit. Nevertheless, under specific activation states, microglia can participate in cerebral amyloid clearance. This review focuses on the complex relationship between microglia and Aβ pathology, and highlights both deleterious and beneficial roles of microglial activation states in the context of AD. A deeper understanding of microglial biology will hopefully pave the way for next-generation AD therapeutic approaches aimed at harnessing these enigmatic innate immune cells of the central nervous system.
Export Options
About this article
Cite this article as:
Guillot-Sestier Marie-Victoire and Town Terrence, Innate Immunity in Alzheimer’s Disease: A Complex Affair, CNS & Neurological Disorders - Drug Targets 2013; 12 (5) . https://dx.doi.org/10.2174/1871527311312050008
DOI https://dx.doi.org/10.2174/1871527311312050008 |
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
-
Viral-Mediated Gene Transfer for Cancer Treatment
Current Pharmaceutical Biotechnology Bioactive N-Phenylimidazole Derivatives
Current Chemical Biology Cerebral Amyloidoses: Molecular Pathways and Therapeutic Challenges
Current Medicinal Chemistry The Forkhead Transcription Factor FOXO3a Controls Microglial Inflammatory Activation and Eventual Apoptotic Injury through Caspase 3
Current Neurovascular Research CIITA and the MHCII Enhanceosome in the Regulation of MHCII Expression
Current Genomics Recombinant Rhabdoviruses as Potential Vaccines for HIV-1 and Other Diseases
Current HIV Research Targeted Oncolytic Herpes Simplex Viruses for Aggressive Cancers
Current Pharmaceutical Biotechnology Molecular Approach to Targeted Therapy for Multiple Sclerosis
CNS & Neurological Disorders - Drug Targets Proteases in Mosquito Borne Diseases: New Avenues in Drug Development
Current Topics in Medicinal Chemistry Tackling COVID-19 Through Ayurveda: A Review on the Herbs of Recommended Indian Remedies
Current Traditional Medicine Editorial [Hot Topic: Tropical Neurology (Guest Editor: Terezinha C.B. Montelli)]
Central Nervous System Agents in Medicinal Chemistry Virus Diagnostics on Microarrays
Current Pharmaceutical Biotechnology A Case Presentation of Atypical X-linked Adrenoleukodystrophy: Initial Experience with ASL Technique
Current Medical Imaging The Herpesvirus Encoded dUTPase as a Potential Chemotherapeutic Target
Current Protein & Peptide Science Peptides as Signaling Inhibitors for Mammalian MAP Kinase Cascades
Current Pharmaceutical Design Multimodality Imaging in Acute Ischemic Stroke
Current Medical Imaging Trends and Applications of Brain Computer Interfaces
Current Signal Transduction Therapy Vaccine Safety Monitoring Systems in Developing Countries: An Example of the Vietnam Model
Current Drug Safety Small Ruminant Lentiviruses and Human Immunodeficiency Virus: Cousins that Take a Long View
Current HIV Research Nose-to-Brain Drug Delivery by Nanoparticles in the Treatment of Neurological Disorders
Current Medicinal Chemistry