Abstract
Inflammation in the central nervous system (CNS) may occur as a result of trauma, infection or neurodegenerative stimuli and is characterized by activation of microglia, the resident immune cells of the CNS. Activated microglia proliferate rapidly, migrate to the site of injury or infection and elicit immune response by phagocytosis of cell debris, production of cytokines, chemokines and reactive oxygen species, and presentation of antigens to other immune cells. In addition, microglia participate in tissue repair by producing neurotrophic factors. However, when microglia are chronically activated, they become neurotoxic to the surrounding CNS parenchyma.
Chronic activation of microglia has been shown to augment neurodegeneration in Parkinson’s disease (PD), Alzheimer’s disease (AD), brain injury and number of other CNS pathologies. Identification of factors that control microglial activation, therefore, has become the major focus of recent research. A number of herbal and chemical compounds have been shown to attenuate microglial activation. However, these compounds exhibit non-specificity and produce unpleasant side-effects. Here, we provide a comprehensive review on some of the currently available drugs known to reduce microglial activation, their molecular targets and the subcellular signaling networks on which they act. We also review some of the newly emerging therapeutic avenues such as ‘epidrugs’ and finally emphasize on the importance of targeted drug delivery systems for alleviating microglia-mediated neurotoxicity.
Keywords: Microglia, inflammation, brain injury, neurodegeneration, retinoic acid, glucocorticoids, minocycline, miRNA, epigenetics.
CNS & Neurological Disorders - Drug Targets
Title:Potential Drugs Targeting Microglia: Current Knowledge and Future Prospects
Volume: 12 Issue: 6
Author(s): Parakalan Rangarajan, Ling Eng-Ang and S. Thameem Dheen
Affiliation:
Keywords: Microglia, inflammation, brain injury, neurodegeneration, retinoic acid, glucocorticoids, minocycline, miRNA, epigenetics.
Abstract: Inflammation in the central nervous system (CNS) may occur as a result of trauma, infection or neurodegenerative stimuli and is characterized by activation of microglia, the resident immune cells of the CNS. Activated microglia proliferate rapidly, migrate to the site of injury or infection and elicit immune response by phagocytosis of cell debris, production of cytokines, chemokines and reactive oxygen species, and presentation of antigens to other immune cells. In addition, microglia participate in tissue repair by producing neurotrophic factors. However, when microglia are chronically activated, they become neurotoxic to the surrounding CNS parenchyma.
Chronic activation of microglia has been shown to augment neurodegeneration in Parkinson’s disease (PD), Alzheimer’s disease (AD), brain injury and number of other CNS pathologies. Identification of factors that control microglial activation, therefore, has become the major focus of recent research. A number of herbal and chemical compounds have been shown to attenuate microglial activation. However, these compounds exhibit non-specificity and produce unpleasant side-effects. Here, we provide a comprehensive review on some of the currently available drugs known to reduce microglial activation, their molecular targets and the subcellular signaling networks on which they act. We also review some of the newly emerging therapeutic avenues such as ‘epidrugs’ and finally emphasize on the importance of targeted drug delivery systems for alleviating microglia-mediated neurotoxicity.
Export Options
About this article
Cite this article as:
Rangarajan Parakalan, Eng-Ang Ling and Thameem Dheen S., Potential Drugs Targeting Microglia: Current Knowledge and Future Prospects, CNS & Neurological Disorders - Drug Targets 2013; 12 (6) . https://dx.doi.org/10.2174/18715273113126660175
DOI https://dx.doi.org/10.2174/18715273113126660175 |
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
-
11C-verapamil to Assess P-gp Function in Human Brain During Aging,Depression and Neurodegenerative Disease
Current Topics in Medicinal Chemistry Vascular Pharmacotherapy and Dementia
Current Vascular Pharmacology Complex and Differential Glial Responses in Alzheimer´s Disease and Ageing
Current Alzheimer Research Microbial Interaction of Periodontopathic Bacterium Porphyromonas gingivalis and HIV-Possible Causal Link of Periodontal Diseases to AIDS Progression-
Current HIV Research Current Evidence and Future Perspectives on Anti-platelet and Statin Pharmacotherapy for Patients with Symptomatic Peripheral Arterial Disease
Current Vascular Pharmacology Genetics and Gene Therapy of Anderson-Fabry Disease
Current Gene Therapy Editorial (Thematic Issue: New Therapeutic Targets in Clinical Medicine)
Current Pharmaceutical Design Pyroglutamate-Modified Amyloid Beta Peptides: Emerging Targets for Alzheimer´s Disease Immunotherapy
Current Neuropharmacology Key Advances in MIP-based Sensors Applied for Cancer and Cardiovascular Biomarkers Detection
Current Topics in Medicinal Chemistry Hereditary Haemorrhagic Teleangiectasia: Diagnostic Imaging of Visceral Involvement
Current Pharmaceutical Design Diabetes and Complications: Cellular Signaling Pathways, Current Understanding and Targeted Therapies
Current Drug Targets Loss of Medial Septum Cholinergic Neurons in THY-Tau22 Mouse Model: What Links with tau Pathology?
Current Alzheimer Research Commentary [Research Highlights : Neurotrophic Factor Treatment of Neurological Disorders: The Benefits of a Pleiotropic Treatment Approach]
CNS & Neurological Disorders - Drug Targets Inflammatory Risk Factors and Pathologies Associated with Alzheimers Disease
Current Alzheimer Research Caregiver Burden in Fragile X Families
Current Psychiatry Reviews Subject Index To Volume 1
Recent Patents on Cardiovascular Drug Discovery To Cardiovascular Disease and Beyond: New Therapeutic Perspectives of Statins in Autoimmune Diseases and Cancer
Current Drug Targets The Safety, Tolerability, Pharmacokinetics and Cognitive Effects of GSK239512, a Selective Histamine H<sub>3</sub> Receptor Antagonist in Patients with Mild to Moderate Alzheimer’s Disease: A Preliminary Investigation
Current Alzheimer Research Nanostructures for Drug Delivery to the Brain
Current Medicinal Chemistry Editorial (Thematic Issue:Drug-eluting Stents and Concomitant Treatment)
Cardiovascular & Hematological Disorders-Drug Targets