Abstract
Alzheimers disease (AD) is a neurodegenerative disease with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Neuroinflammation is involved in the onset of several neurodegenerative disorders. Astrocyte is the most abundant type of glial cells in the central nervous system (CNS) and appears to be involved in the induction of neuroinflammation. Under stress and injury, astrocytes become astrogliotic leading to an upregulation of the expression of proinflammatory cytokines and chemokines, which are associated with the pathogenesis of AD. Cytokines and related molecules play roles in both neuroprotection and neurodegeneration in the CNS. During early AD pathogenesis, amyloid beta (Aβ), S100B and IL-1β could bring about a vicious cycle of Aβ generation between astrocytes and neurons leading to chronic, sustained and progressive neuroinflammation. In advanced stages of AD, TRAIL secreted from astrocytes have been shown to bind to death receptor 5 (DR5) on neurons to trigger apoptosis in a caspase-8-dependent manner. Furthermore, astrocytes could be reactivated by TGFβ1 to generate more Aβ and to undergo the aggravating astrogliosis. TGFβ2 was also observed to cooperate with Aβ to cause neuronal demise by destroying the stability of lysosomes in neurons. Inflammatory molecules can be either potential biomarkers for diagnosis or target molecules for therapeutic intervention. Understanding their roles and their relationship with activated astrocytes is particularly important for attenuating neuroinflammation in the early stage of AD. The main purpose of this review is to provide a comprehensive insight into the role of astrocytes in the neuroinflammatory pathogenesis of AD.
Keywords: Alzheimer's disease, astrocyte, inflammation, cytokine, chemokine, amyloid beta, death receptor, TRAIL, Amyloid precursor protein, alpha secretase, IP-10, MCP-1, S100B, microglia
Current Alzheimer Research
Title: Astrocytes: Implications for Neuroinflammatory Pathogenesis of Alzheimers Disease
Volume: 8 Issue: 1
Author(s): Chuanyu Li, Rui Zhao, Kai Gao, Zheng Wei, Michael Yaoyao Yin, Lok Ting Lau, Dehua Chui and Albert Cheung Hoi Yu
Affiliation:
Keywords: Alzheimer's disease, astrocyte, inflammation, cytokine, chemokine, amyloid beta, death receptor, TRAIL, Amyloid precursor protein, alpha secretase, IP-10, MCP-1, S100B, microglia
Abstract: Alzheimers disease (AD) is a neurodegenerative disease with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Neuroinflammation is involved in the onset of several neurodegenerative disorders. Astrocyte is the most abundant type of glial cells in the central nervous system (CNS) and appears to be involved in the induction of neuroinflammation. Under stress and injury, astrocytes become astrogliotic leading to an upregulation of the expression of proinflammatory cytokines and chemokines, which are associated with the pathogenesis of AD. Cytokines and related molecules play roles in both neuroprotection and neurodegeneration in the CNS. During early AD pathogenesis, amyloid beta (Aβ), S100B and IL-1β could bring about a vicious cycle of Aβ generation between astrocytes and neurons leading to chronic, sustained and progressive neuroinflammation. In advanced stages of AD, TRAIL secreted from astrocytes have been shown to bind to death receptor 5 (DR5) on neurons to trigger apoptosis in a caspase-8-dependent manner. Furthermore, astrocytes could be reactivated by TGFβ1 to generate more Aβ and to undergo the aggravating astrogliosis. TGFβ2 was also observed to cooperate with Aβ to cause neuronal demise by destroying the stability of lysosomes in neurons. Inflammatory molecules can be either potential biomarkers for diagnosis or target molecules for therapeutic intervention. Understanding their roles and their relationship with activated astrocytes is particularly important for attenuating neuroinflammation in the early stage of AD. The main purpose of this review is to provide a comprehensive insight into the role of astrocytes in the neuroinflammatory pathogenesis of AD.
Export Options
About this article
Cite this article as:
Li Chuanyu, Zhao Rui, Gao Kai, Wei Zheng, Yaoyao Yin Michael, Ting Lau Lok, Chui Dehua and Cheung Hoi Yu Albert, Astrocytes: Implications for Neuroinflammatory Pathogenesis of Alzheimers Disease, Current Alzheimer Research 2011; 8 (1) . https://dx.doi.org/10.2174/156720511794604543
DOI https://dx.doi.org/10.2174/156720511794604543 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
Antioxidant Status and Energy State of Erythrocytes in Alzheimer Dementia: Probing for Markers
CNS & Neurological Disorders - Drug Targets Abnormal Sleep Behaviours Across the Spectrum of Alzheimer’s Disease Severity: Influence of APOE Genotypes and Lewy Bodies
Current Alzheimer Research SIRT1, a Calorie Restriction Mimetic, in a New Therapeutic Approach for Type 2 Diabetes Mellitus and Diabetic Vascular Complications
Endocrine, Metabolic & Immune Disorders - Drug Targets Mechanisms of HIV-1 Neurotropism
Current HIV Research The Histamine H3 Receptor as a Therapeutic Drug Target for Metabolic Disorders: Status, Challenges and Opportunities
Current Topics in Medicinal Chemistry Induction of Molecular Chaperones as a Therapeutic Strategy for the Polyglutamine Diseases
Current Pharmaceutical Biotechnology Current Therapeutic Advances in Patients and Experimental Models of Huntington's Disease
Current Drug Targets Tetrahydrobiopterin Pathway may Provide Novel Molecular Targets for Acute and Long Term Efficacy of Mood-Regulating Drugs
Current Pharmacogenomics and Personalized Medicine Alkaloids from Cyanobacteria with Diverse Powerful Bioactivities
Mini-Reviews in Medicinal Chemistry The Prevalence, Morbidities, and Treatments of Insomnia
CNS & Neurological Disorders - Drug Targets The Multimodal Treatment of Acromegaly: Current Status and Future Perspectives
Endocrine, Metabolic & Immune Disorders - Drug Targets Distinctive Effects of Aerobic and Resistance Exercise Modes on Neurocognitive and Biochemical Changes in Individuals with Mild Cognitive Impairment
Current Alzheimer Research Effect of HAART on Salivary Composition and Oxidative Profile in HIVInfected Patients
Current HIV Research Involvement of Cytosolic Phospholipase A2, Calcium Independent Phospholipase A2 and Plasmalogen Selective Phospholipase A2 in Neurodegenerative and Neuropsychiatric Conditions
Current Medicinal Chemistry Lipoxygenase: An Emerging Target for Stroke Therapy
CNS & Neurological Disorders - Drug Targets Enhanced Antioxidant and Protective Activities on Retinal Ganglion Cells of Carotenoids-Overexpressing Transgenic Carrot
Current Drug Targets Neuropsychiatric Involvement in Systemic Lupus Erythematosus:Current Therapeutic Approach
Current Pharmaceutical Design Does Caffeine Affect Cardiovascular Responses?
Vascular Disease Prevention (Discontinued) Non-Demented Individuals with Alzheimer’s Disease Neuropathology: Resistance to Cognitive Decline May Reveal New Treatment Strategies
Current Pharmaceutical Design Miniaturization and Validation of the Ellmans Reaction Based Acetylcholinesterase Inhibitory Assay into 384-Well Plate Format and Screening of a Chemical Library
Combinatorial Chemistry & High Throughput Screening