کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3070453 1580732 2008 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
LRP promotes endocytosis and degradation, but not transcytosis, of the amyloid-β peptide in a blood–brain barrier in vitro model
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
LRP promotes endocytosis and degradation, but not transcytosis, of the amyloid-β peptide in a blood–brain barrier in vitro model
چکیده انگلیسی

The pathogenesis of Alzheimer’s disease is characterized by aggregation of the amyloid-β protein (Aβ) into neurotoxic plaques. Recent in vivo studies have suggested the non-proteolytic clearance of Aβ via receptor-mediated transport across the blood–brain barrier (BBB). The aim of this study was to investigate the role of P-glycoprotein (Pgp) and the low-density lipoprotein receptor-related protein (LRP) in Aβ efflux across the BBB. We developed an in vitro BBB-like model using Madin–Darby Canine Kidney (MDCK) cells seeded on filters separating apical (blood) and basolateral (brain) compartments. MDCK cells were stably transfected with Pgp or mLRP4, an LRP mini-receptor. When compared to empty vector-transfected cells, MDCK-Pgp cells did not transcytose radiolabeled Aβ in the basolateral-to-apical direction. MDCK-mLRP4 cells were found to endocytose and degrade, but not to trasncytose intact radiolabeled Aβ. These results implicate LRP as a mediator of Aβ degradation, but indicate that overexpression of LRP or Pgp alone is insufficient for non-proteolytic transcytosis of intact Aβ.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 30, Issue 1, April 2008, Pages 94–102
نویسندگان
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