Document Detail


Astrocytes as potential targets to suppress inflammatory demyelinating lesions in multiple sclerosis.
MedLine Citation:
PMID:  20178822     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A hallmark of multiple sclerosis (MS) is the occurrence of focal inflammatory demyelinating lesions in the central nervous system. The prevailing view that activated anti-myelin T cells inherently mediate these lesions has been challenged after observations that these T cells, which are part of the normal immune repertoire, can also intermittently become activated in healthy people and subjects with other diseases. Astrocytes in the white matter of subjects with MS are deficient in beta(2) adrenergic receptors. Stimulation of beta(2) adrenergic receptors increases cAMP, leading to activation of protein kinase A (PKA). beta(2) adrenergic receptor deficiency will reduce the suppressive action of PKA on coactivator class II transactivator (CIITA), which is a key regulator of interferon gamma-induced major histocompatibility (MHC) class II molecule transcription. The expression of MHC class II may deviate astrocytes to function as facultative antigen presenting cells, which can then initiate the inflammatory cascade. In a proof of concept study in MS subjects it was shown that fluoxetine, which activates PKA in astrocytes, reduced the development of focal inflammatory lesions. If confirmed and extended by additional studies, suppressing the antigen presenting capacity of astrocytes could be a novel therapeutic option for the treatment of MS.
Authors:
Jacques De Keyser; Guy Laureys; Frauke Demol; Nadine Wilczak; Jop Mostert; Ralph Clinckers
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2010-02-21
Journal Detail:
Title:  Neurochemistry international     Volume:  57     ISSN:  1872-9754     ISO Abbreviation:  Neurochem. Int.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-06     Completed Date:  2010-12-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  446-50     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Neurology, University Hospital Brussel, Vrije Universiteit Brussel, Brussels, Belgium. Jacques.DeKeyser@uzbrussel.be
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MeSH Terms
Descriptor/Qualifier:
Animals
Astrocytes / drug effects*,  metabolism,  pathology*
Demyelinating Diseases / drug therapy*,  pathology*
Humans
Immune Tolerance / physiology
Inflammation / drug therapy*,  pathology*
Multiple Sclerosis / drug therapy*,  pathology*
Receptors, Adrenergic, alpha-1 / physiology
Chemical
Reg. No./Substance:
0/Receptors, Adrenergic, alpha-1

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