| Complement in the brain. | |
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MedLine Citation:
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PMID: 21546088 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The brain is considered to be an immune privileged site, because the blood-brain barrier limits entry of blood borne cells and proteins into the central nervous system (CNS). As a result, the detection and clearance of invading microorganisms and senescent cells as well as surplus neurotransmitters, aged and glycated proteins, in order to maintain a healthy environment for neuronal and glial cells, is largely confined to the innate immune system. In recent years it has become clear that many factors of innate immunity are expressed throughout the brain. Neuronal and glial cells express Toll like receptors as well as complement receptors, and virtually all complement components can be locally produced in the brain, often in response to injury or developmental cues. However, as inflammatory reactions could interfere with proper functioning of the brain, tight and fine tuned regulatory mechanisms are warranted. In age related diseases, such as Alzheimer's disease (AD), accumulating amyloid proteins elicit complement activation and a local, chronic inflammatory response that leads to attraction and activation of glial cells that, under such activation conditions, can produce neurotoxic substances, including pro-inflammatory cytokines and oxygen radicals. This process may be exacerbated by a disturbed balance between complement activators and complement regulatory proteins such as occurs in AD, as the local synthesis of these proteins is differentially regulated by pro-inflammatory cytokines. Much knowledge about the role of complement in neurodegenerative diseases has been derived from animal studies with transgenic overexpressing or knockout mice for specific complement factors or receptors. These studies have provided insight into the potential therapeutic use of complement regulators and complement receptor antagonists in chronic neurodegenerative diseases as well as in acute conditions, such as stroke. Interestingly, recent animal studies have also indicated that complement activation products are involved in brain development and synapse formation. Not only are these findings important for the understanding of how brain development and neural network formation is organized, it may also give insights into the role of complement in processes of neurodegeneration and neuroprotection in the injured or aged and diseased adult central nervous system, and thus aid in identifying novel and specific targets for therapeutic intervention. |
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Authors:
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Robert Veerhuis; Henrietta M Nielsen; Andrea J Tenner |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review Date: 2011-05-04 |
Journal Detail:
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Title: Molecular immunology Volume: 48 ISSN: 1872-9142 ISO Abbreviation: Mol. Immunol. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-07-22 Completed Date: 2011-09-20 Revised Date: 2012-02-21 |
Medline Journal Info:
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Nlm Unique ID: 7905289 Medline TA: Mol Immunol Country: England |
Other Details:
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Languages: eng Pagination: 1592-603 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands. R.Veerhuis@vumc.nl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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immunology Animals Blood-Brain Barrier / immunology Brain / immunology* Brain Injuries / immunology Complement System Proteins / metabolism* Humans Immunity, Innate Mice Models, Immunological Models, Neurological Multiple Sclerosis / immunology Neurodegenerative Diseases / immunology Neuroglia / immunology Neurons / immunology |
| Grant Support | |
ID/Acronym/Agency:
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AG 00538/AG/NIA NIH HHS; NS35144/NS/NINDS NIH HHS; R01 NS035144-12/NS/NINDS NIH HHS; R01 NS035144-13/NS/NINDS NIH HHS; R01 NS035144-14/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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9007-36-7/Complement System Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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