Document Detail


Vascular nitric oxide, sex hormone replacement, and fish oil may help to prevent Alzheimer's disease by suppressing synthesis of acute-phase cytokines.
MedLine Citation:
PMID:  10616034     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The neurodegenerative plaques of Alzheimer's disease (AD) are characterized by a self-sustaining acute-phase reaction in which both interleukin-1 (IL-1) and interleukin-6 (IL-6) are up-regulated. The fact that IL-6 is detectable in early stage diffuse plaques encourages the speculation that the acute-phase process is crucial to the pathogenesis of AD. The epidemiological association of AD with estrogen deficiency, as well as with various disorders characterized by vascular endotheliopathy, suggest a protective role for vascular nitric oxide (NO). NO has an autocrine anti-inflammatory impact on endothelium, owing in part to antagonism of NF-kappaB activity; since induction of IL-6 is dependent on NF-kappaB, this may explain recent evidence that NO inhibits macrophage IL-6 production. It is reasonable to postulate that, analogously, cerebrovascular NO decreases IL-6 production in the brain. Vascular NO may also have direct neuroprotective activity. Estrogen, in addition to promoting vascular NO synthesis, can block IL-6 production by a more direct mechanism in cells expressing estrogen receptors; since such receptors have been reported in brain glia and astrocytes, estrogen has the potential to limit brain IL-1 activity. Testosterone likewise can inhibit IL-6 induction in androgen-responsive cells, which may include brain glia and astrocytes. Since fish oil and gamma linolenic acid (GLA) suppress IL-1 production by stimulated monocytes, they conceivably could exert this effect in the brain as well; the comparatively low prevalence of AD in elderly Japanese is intriguing in this regard. These considerations suggest that a healthy cerebrovascular endothelium, sex hormone activity, and dietary fish oil/GLA may slow or prevent AD onset by dampening acute-phase mechanisms in the brain.
Authors:
M F McCarty
Related Documents :
9576614 - Myoblasts produce il-6 in response to inflammatory stimuli.
8112434 - Regulation of cytokine secretion by cystic fibrosis airway epithelial cells.
11751424 - Il-6 inhibits apoptosis and retains oxidative dna lesions in human gastric cancer ags c...
20519164 - Cytokine profiling of human peripheral blood cd4+ t lymphocytes reveals a new th-subpop...
24368084 - The use of eugenol against aeromonas hydrophila and its effect on hematological and imm...
22036624 - Inhibitory effects of salvianolic acid b on apoptosis of schwann cells and its mechanis...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Medical hypotheses     Volume:  53     ISSN:  0306-9877     ISO Abbreviation:  Med. Hypotheses     Publication Date:  1999 Nov 
Date Detail:
Created Date:  2000-01-20     Completed Date:  2000-01-20     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  7505668     Medline TA:  Med Hypotheses     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  369-74     Citation Subset:  IM    
Affiliation:
Nutrition 21/AMBI, San Diego, CA, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / prevention & control*
Blood Vessels / metabolism
Dihydrotestosterone / administration & dosage,  pharmacology
Down-Regulation / drug effects
Estradiol / administration & dosage,  pharmacology
Fish Oils / pharmacology,  therapeutic use*
Hormone Replacement Therapy*
Humans
Interleukin-1 / antagonists & inhibitors*,  biosynthesis
Interleukin-6 / antagonists & inhibitors*,  biosynthesis
Nitric Oxide / physiology*
Chemical
Reg. No./Substance:
0/Fish Oils; 0/Interleukin-1; 0/Interleukin-6; 10102-43-9/Nitric Oxide; 50-28-2/Estradiol; 521-18-6/Dihydrotestosterone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Does bone perfusion/reperfusion initiate bone remodeling and the stress fracture syndrome?
Next Document:  Niacin as a potential AIDS preventive factor.