PNAS：跨越血脑屏障 带来治疗的新革命
血脑屏障一直是许多中枢系统疾病治疗的重要难点，许多药物都因为无法在脑内形成有效的血药浓度，从而使治疗效果大大下降。
刚刚在本期PNAS上，以色列科学家Vivian I. Teichberg发现一种全新的方法，使透过血脑屏障变得简单，这一方法如何大规模应用，将开创中枢神经系统疾病治疗的革命，尤其是象蛋白质类的大分子。研究表明，在血脑屏障上有一些受体，如果某些蛋白质能很好地与这些受体结合，那么就容易被输入到中枢神经系统内。因此，以色列科学家便寻找一种能与血脑屏障上受体结合的新的治疗手段。作用使用慢病毒（lentivirus)载体系统，将溶酶体的一种酶---β-葡萄糖脑苷脂酶(β-glucocerebrosidase)和分泌状态的GFP制成融合蛋白，发现能成功在肝脏和脑中得到表达。进一步，再融合了低密度脂蛋白受体结合域到此蛋白，进一步促进了蛋白透过血脑屏障进入大脑。为此，PNAS专门为此文发表了相关的评论，高度评价了，这一治疗方法的重要意义与价值。
原始出处:
Published online before print April 26, 2007, 10.1073/pnas.0702450104
PNAS | May 1, 2007 | vol. 104 | no. 18 | 7315-7316
Vivian I. Teichberg*
Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel
The burden of brain diseases as established by a recent report of the World Health Organization represents 30% of the total burden of all diseases. This surprisingly high number is clearly related to the fact that the presently available CNS drugs treat only an extremely small percentage of brain diseases, leaving untreated major disorders, such as Alzheimer's disease, brain cancer, and stroke, or minor ones, such as autism, inherited mental retardation, and ataxia. There are also relatively few CNS drugs, although not for a lack of trying. In fact, ceaseless efforts have been made by the pharmaceutical industry to develop CNS drugs, but the number of failures has unfortunately paralleled the thousands of drugs that have been designed and tested. A major stumbling block has remained the fact that very few drugs have the ability to cross the blood–brain barrier (BBB) and reach their targets within the brain parenchyma (1). The BBB is created by the endothelial cells that provide the walls of the blood vessels perfusing the brain. However, in contrast to the peripheral endothelium, the brain endothelial cells lack capillary fenestrations, display low pinocytic activity, and form very tight junctions that are highly resistant to transendothelial ionic fluxes and strictly limit the entrance of endogenous and exogenous compounds into the CNS. How to successfully negotiate the barrier has required a deep understanding of its intimate properties and a great deal of ingenuity. The paper by Spencer and Verma (2) in this issue of PNAS is a good example of the latter with some extra creativity. To fully appreciate its novelty, . . . [Full Text of this Article]
*E-mail: vivian.teichberg@weizmann.ac.il
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