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

Jae Hoon Moon, Hyung Jun Kim, Ae Hee Yang, Hyun Min Kim, byungwan lee, Eun Seok Kang, Hyun Chul Lee, Bong Soo Cha

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)135-142
Number of pages8
JournalInternational Journal of Neuropsychopharmacology
Volume15
Issue number1
DOIs
Publication statusPublished - 2012 Feb 1

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rosiglitazone
Amyloid
Dementia
Endothelial Cells
Brain
Thiazolidinediones
Alzheimer Disease
pioglitazone
Blood-Brain Barrier
Human Activities
2,4-thiazolidinedione
Anti-Inflammatory Agents
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

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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.",
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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. / Moon, Jae Hoon; Kim, Hyung Jun; Yang, Ae Hee; Kim, Hyun Min; lee, byungwan; Kang, Eun Seok; Lee, Hyun Chul; Cha, Bong Soo.

In: International Journal of Neuropsychopharmacology, Vol. 15, No. 1, 01.02.2012, p. 135-142.

Research output: Contribution to journalArticle

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AU - Kim, Hyung Jun

AU - Yang, Ae Hee

AU - Kim, Hyun Min

AU - lee, byungwan

AU - Kang, Eun Seok

AU - Lee, Hyun Chul

AU - Cha, Bong Soo

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