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The effect of rosiglitazone on LRP1 expression and amyloid β uptake in human brain microvascular endothelial cells: a possible role of a low-dose thiazolidinedione for dementia treatment.

Authors
 Jae Hoon Moon  ;  Hyung Jun Kim  ;  Ae Hee Yang  ;  Hyun Min Kim  ;  Byung-Wan Lee  ;  Eun Seok Kang  ;  Hyun Chul Lee  ;  Bong Soo Cha 
Citation
 INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, Vol.15(1) : 135-142, 2012 
Journal Title
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
ISSN
 1461-1457 
Issue Date
2012
MeSH
Amyloid beta-Peptides/metabolism* ; Anti-Inflammatory Agents/administration & dosage ; Blood-Brain Barrier/drug effects ; Blood-Brain Barrier/physiopathology ; Brain/blood supply ; Brain/drug effects* ; Brain/physiopathology ; Dose-Response Relationship, Drug ; Endothelial Cells/drug effects* ; Endothelial Cells/physiology ; Gene Expression/drug effects ; Humans ; Low Density Lipoprotein Receptor-Related Protein-1/genetics ; Low Density Lipoprotein Receptor-Related Protein-1/metabolism* ; Microvessels/drug effects ; Microvessels/physiopathology ; Neuroprotective Agents/administration & dosage* ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Thiazolidinediones/administration & dosage*
Keywords
Amyloid beta-Peptides/metabolism* ; Anti-Inflammatory Agents/administration & dosage ; Blood-Brain Barrier/drug effects ; Blood-Brain Barrier/physiopathology ; Brain/blood supply ; Brain/drug effects* ; Brain/physiopathology ; Dose-Response Relationship, Drug ; Endothelial Cells/drug effects* ; Endothelial Cells/physiology ; Gene Expression/drug effects ; Humans ; Low Density Lipoprotein Receptor-Related Protein-1/genetics ; Low Density Lipoprotein Receptor-Related Protein-1/metabolism* ; Microvessels/drug effects ; Microvessels/physiopathology ; Neuroprotective Agents/administration & dosage* ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Thiazolidinediones/administration & dosage*
Abstract
Thiazolidinediones, such as rosiglitazone or pioglitazone, are anti-diabetic agents that have been expected to show a beneficial effect in Alzheimer's disease (AD) because of their anti-inflammatory effect. However, these agents have failed to show a significant beneficial effect on AD in recent clinical trials. Here, we suggest that low-dose rosiglitazone treatment, and not the conventional doses, has an amyloid β (Aβ)-clearing effect by increasing LRP1, an Aβ outward transporter in the blood-brain barrier. Rosiglitazone up-regulated LRP1 mRNA and protein expression and LRP1 promoter activity in human brain microvascular endothelial cells (HBMECs). Aβ uptake through LRP1 in HBMECs was also increased by rosiglitazone. This increase in LRP1 and Aβ uptake was observed in up to 10 nm rosiglitazone concentration. At concentrations above 20 nm rosiglitazone, the LRP1 expression and Aβ uptake in HBMECs were not altered. The possible mechanism of this unusual dose response is discussed. This study suggests a new therapeutic application of thiazolidinediones for AD at a much lower dose than the doses used for diabetes treatment.
Full Text
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8465540
DOI
22040807
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Kim, Hyun Min(김현민)
Moon, Jae Hoon(문재훈)
Yang, Ae Hee(양애희)
Lee, Byung Wan(이병완) ORCID logo https://orcid.org/0000-0002-9899-4992
Lee, Hyun Chul(이현철)
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90498
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