NDLI: Major Involvement of Low-Density Lipoprotein Receptor-Related Protein 1 in the Clearance of Plasma Free Amyloid β-Peptide by the Liver

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Major Involvement of Low-Density Lipoprotein Receptor-Related Protein 1 in the Clearance of Plasma Free Amyloid β-Peptide by the Liver

Content Provider	Springer Nature Link
Author	Tamaki, Chihiro Ohtsuki, Sumio Iwatsubo, Takeshi Hashimoto, Tadafumi Yamada, Kaoru Yabuki, Chiori Terasaki, Tetsuya
Copyright Year	2006
Abstract	To identify the molecules responsible for amyloid β-peptide (1–40) (Aβ(1–40)) uptake by the liver, which play a major role in the systemic clearance of Aβ(1–40).The liver uptake index method was used to examine the mechanisms of Aβ(1–40) uptake by the liver in vivo.[$^{125}$I]Aβ(1–40) uptake by the rat liver was concentration-dependent (50% saturation concentration = 302 nM). The inhibitory spectrum of Aβ fragments indicated that 17–24 in Aβ (LVFFAEDV) was the putative sequence responsible for hepatic Aβ(1–40) uptake. Receptor-associated protein (RAP) inhibited [$^{125}$I]Aβ(1–40) uptake by 48%. RAP-deficient mice, in which low-density lipoprotein receptor-related protein 1 (LRP-1) expression was suppressed, showed a 46% reduction in [$^{125}$I]Aβ(1–40) uptake by the liver. siRNA-mediated suppression of LRP-1 expression in the liver resulted in a reduction in [$^{125}$I]Aβ(1–40) uptake by 64%. Both the expression of LRP-1 in the liver and the hepatic Aβ(1–40) uptake were significantly reduced in 13-month-old rats compared with 7-week-old rats.LRP-1 is the major receptor responsible for the saturable uptake of plasma free Aβ(1–40) by the liver. Reduction of LRP-1 expression will play a role in the age-related reduction in hepatic Aβ(1–40) clearance.
Starting Page	1407
Ending Page	1416
Page Count	10
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	23
Issue Number	7
e-ISSN	1573904X
Language	English
Publisher	Springer-Verlag
Publisher Date	2006-06-21
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	amyloid β-peptide clearance liver uptake index low-density lipoprotein receptor-related protein 1 receptor-mediated endocytosis Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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