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 language | English |
|---|---|
| Pages (from-to) | 135-142 |
| Number of pages | 8 |
| Journal | International Journal of Neuropsychopharmacology |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2012 Feb 1 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
- Psychiatry and Mental health
- Pharmacology (medical)
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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 journal › Article
TY - JOUR
T1 - The effect of rosiglitazone on LRP1 expression and amyloid β uptake in human brain microvascular endothelial cells
T2 - A possible role of a low-dose thiazolidinedione for dementia treatment
AU - Moon, Jae Hoon
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
PY - 2012/2/1
Y1 - 2012/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84856492410&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856492410&partnerID=8YFLogxK
U2 - 10.1017/S1461145711001611
DO - 10.1017/S1461145711001611
M3 - Article
C2 - 22040807
AN - SCOPUS:84856492410
VL - 15
SP - 135
EP - 142
JO - International Journal of Neuropsychopharmacology
JF - International Journal of Neuropsychopharmacology
SN - 1461-1457
IS - 1
ER -