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血脑屏障的结构及其在跨屏障底物转运体中的作用。

Structure of the Blood Brain Barrier and its Role in the Transporters for the Movement of Substrates across the Barriers.

机构信息

Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, 603203, India.

出版信息

Curr Drug Metab. 2023;24(4):250-269. doi: 10.2174/1389200224666230608110349.

Abstract

For the brain to operate normally and to develop with structural integrity in addition to neuronal function, blood-brain barrier present in brain capillaries serves as a vital barrier mechanism. In addition to the transport barrier created by membranes, transporters, and vesicular processes, the structure and function of the BBB are summarised. The physical barrier is created by endothelial tight junctions. The permeability and transport of molecules between extracellular fluid and plasma are constrained by the presence of tight junctions between neighbouring endothelial cells. Each solute must pass through both membranes in the luminal and abluminal divisions. The functions of the neurovascular unit are described, with special emphasis on the pericytes, microglia, and astrocyte endfeet. The luminal membrane contains five separate facilitative transport mechanisms, each of which is exclusive to a few substrates. Nevertheless, the import of big-branched and aromatic neutral amino acids is facilitated by two key carriers (System L and y+) in the plasma membrane. It is asymmetrically present in both membranes. The sodium pump Na/K-ATPase is highly expressed in the abluminal membrane, where many Na dependent transport mechanisms move amino acids against its concentration gradient. The trojan horse strategy, which uses molecular tools to bind the medication and its formulations, is also preferred in drug delivery. The BBB's cellular structure, the transport systems unique to each substrate, and the necessity to identify transporters with changes that assist the transfer of various medications have all been changed in the current work. Nevertheless, to rule out the BBB passage for the new class of neuroactive medications, the mixing of traditional pharmacology and nanotechnology needs to be focused on outcomes that show promise.

摘要

为了使大脑正常运作并保持结构完整,除了神经元功能外,存在于脑毛细血管中的血脑屏障充当着重要的屏障机制。除了由膜、转运体和囊泡过程创建的转运屏障外,还总结了 BBB 的结构和功能。物理屏障是由内皮紧密连接形成的。相邻内皮细胞之间紧密连接的存在限制了分子在细胞外液和血浆之间的通透性和转运。每种溶质都必须穿过腔侧和基底膜。描述了神经血管单元的功能,特别强调了周细胞、小胶质细胞和星形胶质细胞终足。腔膜包含五个单独的易化转运机制,每个机制都只对少数底物具有专一性。然而,大支链和芳香族中性氨基酸的输入是由质膜中的两个关键载体(System L 和 y+)促进的。它在两个膜中都是不对称存在的。钠泵 Na/K-ATPase 在基底膜中高度表达,许多 Na 依赖的转运机制将氨基酸逆其浓度梯度转运。利用分子工具将药物与其制剂结合的特洛伊木马策略也常用于药物递送。在当前的工作中,改变了 BBB 的细胞结构、每种底物特有的转运系统以及识别有助于各种药物转运的转运体的必要性。然而,为了排除新的神经活性药物类别的 BBB 通透性,需要将传统药理学和纳米技术的混合集中在有希望的结果上。

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