Heparin oligosaccharides that pass the blood-brain barrier inhibit beta-amyloid precursor protein secretion and heparin binding to beta-amyloid peptide.
Heparin oligosaccharides that pass the blood-brain barrier inhibit beta-amyloid precursor protein secretion and heparin binding to beta-amyloid peptide.
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通过血脑屏障的肝素寡糖抑制β-淀粉样蛋白前体蛋白的分泌以及肝素与β-淀粉样肽的结合。
DOI：
10.1046/j.1471-4159.1998.70020736.x
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发表时间：
1998
影响因子：
4.7
通讯作者：
Fillit,H
中科院分区：
文献类型：
--
作者：
Leveugle,B;Ding,W;Laurence,F;Dehouck,MP;Scanameo,A;Cecchelli,R;Fillit,H
我们之前已经证明，全长肝素通过神经母细胞瘤细胞中的淀粉样蛋白生成途径刺激β淀粉样前体蛋白（APP）的合成和分泌。在本研究中，对肝素进行化学解聚，并研究了低分子量（LMW）肝素对APP分泌的影响。与全长肝素相比，LMW肝素对APP分泌无显著影响。然而，低分子肝素片段，特别是肝素二糖，能够有效地抑制肝素对APP分泌的刺激作用。低分子量肝素衍生物还可抑制肝素与β淀粉样肽的结合（1-28）。使用体外模型，我们进一步证明了LMW肝素衍生物通过血脑屏障。这项研究表明，低分子肝素衍生物或类似物可能是有效的治疗剂，以防止或减缓淀粉样蛋白的过程中阿尔茨海默氏病。
We have previously demonstrated that full‐length heparin stimulates the synthesis and secretion of β‐amyloid precursor protein (APP) through an amyloidogenic pathway in neuroblastoma cells. In the present study, heparin was chemically depolymerized, and the effect of low‐molecular‐weight (LMW) heparin on APP secretion was investigated. In contrast to full‐length heparin, LMW heparin had no significant effect on APP secretion. However, LMW heparin fragments, especially heparin disaccharides, were able to inhibit efficiently the stimulatory effect of heparin on APP secretion. LMW heparin derivatives also inhibit the binding of heparin to the β‐amyloid peptide (1–28). Using an in vitro model, we further demonstrated the passage of LMW heparin derivatives through the blood‐brain barrier. This study suggests that LMW heparin derivatives or analogues may be effective as therapeutic agents to prevent or slow the process of amyloidogenesis in Alzheimer's disease.