Oatp1a4 and an L-Thyroxine-Sensitive Transporter Mediate the Mouse Blood-Brain Barrier Transport of Amyloid-β Peptide

被引：17

作者：

Do, Tuan Minh ^{[1
]}

Bedussi, Beatrice ^{[2
]}

Chasseigneaux, Stephanie ^{[2
]}

Dodacki, Agnes ^{[2
]}

Yapo, Cedric ^{[2
]}

Chacun, Helene ^{[3
]}

Scherrmann, Jean-Michel ^{[2
]}

Farinotti, Robert ^{[1
]}

Bourasset, Fanchon ^{[2
]}

机构：

[1] Univ Paris 11, Fac Pharm, Lab Pharmacie Clin & Pharmacocinet, EA 4123, F-92290 Chatenay Malabry, France

[2] Univ Paris 05, Sorbonne Paris Cite, Fac Sci Pharmaceut, INSERM U705,CNRS UMR 8206,Univ Paris Diderot, F-75270 Paris, France

[3] Univ Paris 11, Fac Pharm, UMR CNRS 8612, F-92290 Chatenay Malabry, France

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2013年 / 36卷 / 03期

关键词：

Alzheimer's disease; amyloid-beta peptide; blood-brain barrier; in situ brain perfusion; L-thyroxine; Oatp1a4; rosuvastatin; ORGANIC ANION TRANSPORTER; P-GLYCOPROTEIN; ALZHEIMERS-DISEASE; A-BETA; ENDOTHELIAL-CELLS; THYROID-FUNCTION; MODEL; CLEARANCE; EXPRESSION; PROTEIN;

D O I：

10.3233/JAD-121891

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The influx of amyloid-beta peptide (A beta) across the blood-brain barrier is partly mediated by the receptor for advanced glycation end products (RAGE). But other transporters, like Oatp (organic anion transporter polypeptide, SLC21) transporters, could also be involved. We used in situ brain perfusion to show that rosuvastatin and taurocholate, two established Oatp1a4 substrates, decreased (5-fold) the Cl-up of [H-3]A beta while L-thyroxine increased it (5.5-fold). We demonstrated an interaction between A beta and Oatp1a4 by co-immunoprecipitation and western blotting experiments, supporting the hypothesis that the rosuvastatin- and taurocholate-sensitive transporter was Oatp1a4. In conclusion, our results suggest that, in mice, the brain uptake of A beta is partly mediated by Oatp1a4 and that L-thyroxine may play a crucial role in the inhibition of brain A beta clearance.

引用

页码：555 / 561

页数：7

共 44 条

[41] Involvement of multispecific organic anion transporter, Oatp14 (Slc21a14), in the transport of thyroxine across the blood-brain barrier [J].