کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5847963 1561615 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mini-reviewAn alkaline phosphatase transport mechanism in the pathogenesis of Alzheimer's disease and neurodegeneration
ترجمه فارسی عنوان
مینی بررسی مکانیسم انتقال آلکالن فسفاتاز در پاتوژنز بیماری آلزایمر و عصبی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی


- We apply our alkaline phosphatase transport hypothesis to the blood-brain barrier.
- This provides a novel explanation for Aβ and tau pathologies in Alzheimer's disease.
- The system requires transcytosis of alkaline phosphatase in an IgG immune complex.
- This is triggered by inflammation and the neonatal Fc receptor is the carrier.
- We support the mechanistic hypothesis with a solid literature foundation.

Systemic inflammation is associated with loss of blood-brain barrier integrity and neuroinflammation that lead to the exacerbation of neurodegenerative diseases. It is also associated specifically with the characteristic amyloid-β and tau pathologies of Alzheimer's disease. We have previously proposed an immunosurveillance mechanism for epithelial barriers involving negative feedback-regulated alkaline phosphatase transcytosis as an acute phase anti-inflammatory response that hangs in the balance between the resolution and the progression of inflammation. We now extend this model to endothelial barriers, particularly the blood-brain barrier, and present a literature-supported mechanistic explanation for Alzheimer's disease pathology with this system at its foundation. In this mechanism, a switch in the role of alkaline phosphatase from its baseline duties to a stopgap anti-inflammatory function results in the loss of alkaline phosphatase from cell membranes into circulation, thereby decreasing blood-brain barrier integrity and functionality. This occurs with impairment of both amyloid-β efflux and tau dephosphorylating activity in the brain as alkaline phosphatase is replenished at the barrier by receptor-mediated transport. We suggest systemic alkaline phosphatase administration as a potential therapy for the resolution of inflammation and the prevention of Alzheimer's disease pathology as well as that of other inflammation-related neurodegenerative diseases.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 226, 25 January 2015, Pages 30-39
نویسندگان
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