Document Detail


Curcumins Promote Monocytic Gene Expression Related to β-Amyloid and Superoxide Dismutase Clearance.
MedLine Citation:
PMID:  22156608     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Neurodegenerative diseases are associated with accumulation of modified proteins or peptides including amyloid-β (Aβ) in Alzheimer's disease (AD), and misfolded superoxide dismutase-1 (SOD-1) in amyotrophic lateral sclerosis (ALS). Clearance of Aβ or SOD-1 by the innate immune system may be important for controlling or preventing disease onset. Curcumins restore Aβ phagocytosis by peripheral blood mononuclear cells (PBMCs) from AD patients and Aβ clearance with upregulation of key genes including MGAT3, vitamin D receptor (VDR) and Toll-like receptors (TLRs). Certain curcumins inhibit inflammatory processes of PBMCs from ALS patients. We developed an in vitro system using human monocytes from patients and monocytic cell lines (i.e. U-937, THP-1) for evaluating curcuminoid potency of innate immune cell stimulation. Bisdemethoxycurcumin and certain analogs potentiated MGAT3,VDR and TLR gene expression 3- to 300-fold in U-937 cells. The effect of curcumins on inflammation in monocytes from patients with ALS was examined. Recursive medicinal chemistry was applied to identify compounds that stimulate the innate immune system for use in the clearance of Aβ in AD and the reversal of neuroinflammation and defective SOD-1 accumulation in ALS.
Authors:
J R Cashman; S Gagliardi; M Lanier; S Ghirmai; K J Abel; M Fiala
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-07
Journal Detail:
Title:  Neuro-degenerative diseases     Volume:  -     ISSN:  1660-2862     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101189034     Medline TA:  Neurodegener Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
Affiliation:
Human BioMolecular Research Institute, San Diego, Calif., USA.
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