血腦屏障一直是許多中樞系統(tǒng)疾病治療的重要難點,，許多藥物都因為無法在腦內(nèi)形成有效的血藥濃度,，從而使治療效果大大下降,。
剛剛在本期PNAS上,，以色列科學(xué)家Vivian I. Teichberg發(fā)現(xiàn)一種全新的方法,，使透過血腦屏障變得簡單,，這一方法如何大規(guī)模應(yīng)用,，將開創(chuàng)中樞神經(jīng)系統(tǒng)疾病治療的革命，尤其是象蛋白質(zhì)類的大分子,。研究表明,，在血腦屏障上有一些受體，如果某些蛋白質(zhì)能很好地與這些受體結(jié)合,，那么就容易被輸入到中樞神經(jīng)系統(tǒng)內(nèi),。因此，以色列科學(xué)家便尋找一種能與血腦屏障上受體結(jié)合的新的治療手段,。作用使用慢病毒（lentivirus)載體系統(tǒng),，將溶酶體的一種酶---β-葡萄糖腦苷脂酶(β-glucocerebrosidase)和分泌狀態(tài)的GFP制成融合蛋白，發(fā)現(xiàn)能成功在肝臟和腦中得到表達(dá),。進(jìn)一步,，再融合了低密度脂蛋白受體結(jié)合域到此蛋白，進(jìn)一步促進(jìn)了蛋白透過血腦屏障進(jìn)入大腦,。為此,，PNAS專門為此文發(fā)表了相關(guān)的評論，高度評價了,，這一治療方法的重要意義與價值,。
原始出處:
Published online before print April 26, 2007, 10.1073/pnas.0702450104
PNAS | May 1, 2007 | vol. 104 | no. 18 | 7315-7316
From the liver to the brain across the blood–brain barrier
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: [email protected]
