Document Detail


Knockdown of ACAT-1 reduces amyloidogenic processing of APP.
MedLine Citation:
PMID:  17412327     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous studies have shown that acyl-coenzyme A:cholesterol acyl transferase (ACAT), an enzyme that controls cellular equilibrium between free cholesterol and cholesteryl esters, modulates proteolytic processing of APP in cell-based and animal models of Alzheimer's disease. Here we report that ACAT-1 RNAi reduced cellular ACAT-1 protein by approximately 50% and cholesteryl ester levels by 22% while causing a slight increase in the free cholesterol content of ER membranes. This correlated with reduced proteolytic processing of APP and 40% decrease in Abeta secretion. These data show that even a modest decrease in ACAT activity can have robust suppressive effects on Abeta generation.
Authors:
Henri J Huttunen; Christopher Greco; Dora M Kovacs
Related Documents :
6830837 - Influence of diets on acyl-coa:cholesterol acyltransferase and on acyl-coa:retinol acyl...
3241127 - Effects of dietary retinoid and triglyceride on the lipid composition of rat liver stel...
10511297 - Advances in understanding of the role of lecithin cholesterol acyltransferase (lcat) in...
8068007 - Application of simultaneous spleen and liver perfusion to the study of reverse choleste...
8432427 - Persistent dysregulation of iga production and iga nephropathy in the b6c3f1 mouse foll...
2514227 - Dissolution of human brown pigment biliary stones.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-03-30
Journal Detail:
Title:  FEBS letters     Volume:  581     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-10     Completed Date:  2007-06-13     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1688-92     Citation Subset:  IM    
Affiliation:
Neurobiology of Disease Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States. Henri_Huttunen@hms.harvard.edu
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amyloid beta-Peptides / metabolism*
Cholesterol Esters / analysis,  metabolism
Endoplasmic Reticulum / enzymology
Humans
RNA Interference
RNA, Small Interfering / pharmacology
Sterol O-Acyltransferase / antagonists & inhibitors,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
R01 NS045860-05/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Cholesterol Esters; 0/RNA, Small Interfering; EC 2.3.1.26/Sterol O-Acyltransferase; EC 2.3.1.26/sterol O-acyltransferase 1
Comments/Corrections

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


Previous Document:  Inhibition of hepatic glucose 6-phosphatase system by the green tea flavanol epigallocatechin gallat...
Next Document:  Growth-associated protein 43-positive sensory nerve fibers accompanied by immature vessels are locat...