Document Detail


Cytokines, signal transduction, and inflammatory demyelination: review and hypothesis.
MedLine Citation:
PMID:  9482240     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mechanism of focal demyelination in multiple sclerosis has been a long-standing enigma of this disorder. Cytokines, a diverse family of signalling molecules, are viewed as potential mediators of the process based on clinical observations and studies with animal models and tissue/cell culture systems. Myelin and oligodendrocyte (OL) destruction occur in cultured preparations subjected to cytokines such as tumor necrosis factor-alpha (TNF alpha) and lymphotoxin (LT). Many studies have shown these and other cytokines to be elevated at lesion sites and in the CSF of multiple sclerosis (MS) patients, with similar findings in animal models. Some variability in the nature of MS lesion formation has been reported, both OLs and myelin being primary targets. To account for myelin destruction in the presence of apparently functional OLs we hypothesize that cytokines such as TNF alpha and LT alpha contribute to myelin damage through triggering of specific reactions within the myelin sheath. We further propose that neutral sphingomyelinase (SMase) is one such enzyme, two forms of which have been detected in purified myelin. An additional event is accumulation of cholesterol ester, apparently a downstream consequence of cytokine-induced SMase. The resulting lipid changes are viewed as potentially destabilizing to myelin, which may render it more vulnerable to attack by invading and resident phagocytes.
Authors:
R W Ledeen; G Chakraborty
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Neurochemical research     Volume:  23     ISSN:  0364-3190     ISO Abbreviation:  Neurochem. Res.     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1998-03-26     Completed Date:  1998-03-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7613461     Medline TA:  Neurochem Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  277-89     Citation Subset:  IM    
Affiliation:
Department of Neurosciences, New Jersey Medical School, UMDNJ, Newark 07103, USA. ledeenro@umdnj.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Cytokines / physiology*
Demyelinating Diseases / immunology,  metabolism,  pathology*
Humans
Inflammation / immunology,  pathology
Signal Transduction* / immunology
Grant Support
ID/Acronym/Agency:
NS 16181/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines

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