Effect of rosiglitazone on amyloid precursor protein processing and Aβ clearance in streptozotocin-induced rat model of Alzheimer’ s disease

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WANG LI; LIU WEI; Fan Ying; Liu Tingting; Yu Chunjiang

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Journal Paper

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Journal: Iranian Journal of Basic Medical Sciences Year:2017 | Volume:20 | Issue:5 Page(s): 474-480

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Title

Effect of rosiglitazone on amyloid precursor protein processing and Aβ clearance in streptozotocin-induced rat model of Alzheimer’ s disease

Author(s)

Keywords

Alzheimer’

s disease

Amyloid precursor protein–

processing

-amyloid peptide clearance

Peroxisome proliferator-activated receptor γ

Abstract

Objective(s): Increasing evidence suggests that Alzheimer’; s disease (AD) is associated with diabetes. Rosiglitazone, a Peroxisome proliferator-activated receptor γ; (PPAR-γ ) agonist and anti-diabetic agent, may improve symptoms of AD. However, the underlying therapeutic potential of it has not been fully elucidated. Materials and Methods: Rats were divided into four groups: control group, sham operated group, Streptozotocin (STZ) group, rosiglitazone (RGZ) group. Particularly, the STZ-induced rat model was established by intracerebroventricular injection (3 mg/kg) on the first and third day. The water maze behavioral test was performed to evaluate spatial reference learning and memory of the rats. Aβ; 1-40 and Aβ; 1-42 levels were measured by ELISA method. To determine APP-derived fragment, BACE1 and Aβ; degrading enzymes levels, such as NEP and IDE, as well as Aβ; transportation protein level, such as LRP1, RAGE, Abca1 and APOE, which were analyzed by Western blot. Immunohistochemistry was used to observe the change of Aβ; 1-40 and Aβ; 1-42 in hippocampus. Results: Chronic treatment with RGZ could reduce the Aβ; level and improved spatial memory performance in STZ-induced rat model. However, RGZ modified the expression of specific transport proteins monitoring Aβ; clearance, such as ATP-binding cassette transporter 1 (ABCA1), lipoprotein receptor-related protein 1 (LRP1), and the advanced glycation end product-specific receptor (RAGE) rather than change levels of Aβ; degrading enzymes, such as IDE and NEP, nor affect APP processing. Conclusion: As a potential therapeutic strategy, rosiglitazone might exert anti-AD effect not by alteration of APP processing pathway and Aβ; degradation directly, but through promotion of Aβ; clearance indeed.

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APA: Copy

WANG, LI, LIU, WEI, Fan, Ying, Liu, Tingting, & Yu, Chunjiang. (2017). Effect of rosiglitazone on amyloid precursor protein processing and Aβ clearance in streptozotocin-induced rat model of Alzheimer’ s disease. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, 20(5), 474-480. SID. https://sid.ir/paper/725797/en

Vancouver: Copy

WANG LI, LIU WEI, Fan Ying, Liu Tingting, Yu Chunjiang. Effect of rosiglitazone on amyloid precursor protein processing and Aβ clearance in streptozotocin-induced rat model of Alzheimer’ s disease. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES[Internet]. 2017;20(5):474-480. Available from: https://sid.ir/paper/725797/en

IEEE: Copy

LI WANG, WEI LIU, Ying Fan, Tingting Liu, and Chunjiang Yu, “Effect of rosiglitazone on amyloid precursor protein processing and Aβ clearance in streptozotocin-induced rat model of Alzheimer’ s disease,” IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, vol. 20, no. 5, pp. 474–480, 2017, [Online]. Available: https://sid.ir/paper/725797/en

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