演題詳細
Symposium
血液脳関門制御の最新の知見
Recent progress in the regulation of blood-brain barrier (BBB)
開催日 | 2014/9/13 |
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時間 | 15:00 - 17:00 |
会場 | Room E(301) |
Chairperson(s) | 寺崎 哲也 / Tetsuya Terasaki (東北大学大学院薬学研究科 / Department of Biochemical Pharmacology and Therapeutics, Tohoku University, Japan) 横田 隆徳 / Takanori Yokota (東京医科歯科大学 大学院医歯学総合研究科 脳神経病態学分野 / Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Japan) |
脳関門におけるamyloid-β輩出輸送の分子機構
Molecular mechanism of cerebral clearance of human amyloid-β peptide across the blood-brain barrier
- S3-E-2-2
- 大槻 純男 / Sumio Ohtsuki:1 伊藤 慎悟 / Shingo Ito:1 寺崎 哲也 / Tetsuya Terasaki:2
- 1:熊本大院生命科学・微生物 / Fac Life Sci, Kumamoto Univ, Kumamoto, Japan 2:東北大院薬・薬物送達 / Grad Sch Pham Sci, Tohoku Univ, Sendai, Japan
Reduced clearance of cerebral amyloid-β peptide (Aβ) has been proposed to cause accumulation of Aβ in the late-onset Alzheimer's disease (AD) brain. Cerebral clearance of soluble Aβ is mainly achieved by the brain-to-blood efflux transport system at the blood-brain barrier (BBB) and the Aβ-degrading system. Low-density lipoprotein receptor-related protein-1 (LRP-1) has been suggested to be a molecule responsible for the brain-to-blood human Aβ (hAβ) efflux transport at the BBB. However, the extent of contribution of LRP-1, and other reported molecules to the clearance remains controversial. We reported that the BBB did not possess significant LRP-1-mediated brain-to-blood efflux transport activity in mouse and rat cerebral cortex. In contrast, Our previous report demonstrated that hAβ(1-40) elimination from rat brain across the BBB is significantly inhibited by insulin. It has been shown that insulin receptor is expressed in brain capillary endothelial cells, and plays a role in blood-to-brain transcellular transport across the BBB. However, an insulin receptor inhibitor did not inhibit the elimination of hAβ(1-40) from rat brain. These results suggested that an unknown insulin-sensitive process is involved in hAβ(1-40) elimination from the brain, and the molecular mechanism of insulin-sensitive elimination pathway could be important to understand in detail the pathogenesis of AD, and relationship between AD and diabetes. In this lecture, we will present our latest results about the molecular mechanism of BBB transport system involving in the cerebral clearance of h Aβ(1-40).