Isoprenoids and related pharmacological interventions: potential application in Alzheimer's disease.
Isoprenoids and related pharmacological interventions: potential application in Alzheimer's disease.
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DOI：
10.1007/s12035-012-8253-1
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发表时间：
2012-08
影响因子：
5.1
通讯作者：
Parent, Marc
中科院分区：
文献类型：
--
作者：
Li, Ling;Zhang, Wei;Cheng, Shaowu;Cao, Dongfeng;Parent, Marc
关键词：
两种主要的类异戊二烯，法呢基焦磷酸和香叶基香叶基焦磷酸，作为具有特征性C-末端基序的蛋白质的翻译后修饰（称为异戊烯化）的脂质供体。异戊二烯化反应由异戊二烯基转移酶催化。脂质异戊烯基促进蛋白质在细胞膜中的锚并介导蛋白质-蛋白质相互作用。各种重要的细胞内蛋白质经历异戊烯化，包括小G蛋白超家族的几乎所有成员以及异源三聚体G蛋白亚基和核纤层蛋白。这些异戊二烯化蛋白质参与调节广泛的细胞过程和功能，例如细胞生长、分化、细胞骨架组织和囊泡运输。异戊烯化的蛋白质也涉及不同类型疾病的发病机制。因此，类异戊二烯和/或异戊烯基转移酶已经成为对抗各种病症的有吸引力的治疗靶标。这篇综述试图总结目前可用或正在开发的控制类异戊二烯可用性和/或异戊二烯化过程的药理学药物，主要集中在他汀类药物、双膦酸盐和异戊二烯基转移酶抑制剂。他汀类药物和双膦酸盐通过抑制上游酶的活性来消耗类异戊二烯的产生，而异戊烯基转移酶抑制剂直接阻断蛋白质的异戊烯化。随着类异戊二烯和异戊二烯化蛋白质在健康和疾病中的重要性不断显现，这些药理学试剂的治疗潜力已经扩展到多个学科。本文就其在阿尔茨海默病中的应用作一综述。
Two major isoprenoids, farnesyl pyrophosphate and geranylgeranyl pyrophosphate, serve as lipid donors for the posttranslational modification (known as prenylation) of proteins that possess a characteristic C-terminal motif. The prenylation reaction is catalyzed by prenyltransferases. The lipid prenyl group facilitates to anchor the proteins in cell membranes and mediates protein-protein interactions. A variety of important intracellular proteins undergo prenylation, including almost all members of small GTPase superfamilies as well as heterotrimeric G protein subunits and nuclear lamins. These prenylated proteins are involved in regulating a wide range of cell processes and functions, such as cell growth, differentiation, cytoskeletal organization and vesicle trafficking. Prenylated proteins are also implicated in the pathogenesis of different types of diseases. Consequently, isoprenoids and/or prenyltransferases have emerged as attractive therapeutic targets for combating various disorders. This review attempts to summarize the pharmacological agents currently available or under development that control isoprenoid availability and/or the process of prenylation, mainly focusing on statins, bisphosphonates, and prenyltransferase inhibitors. Whereas statins and bisphosphonates deplete the production of isoprenoids by inhibiting the activity of upstream enzymes, prenyltransferase inhibitors directly block the prenylation of proteins. As the importance of isoprenoids and prenylated proteins in health and disease continues to emerge, the therapeutic potential of these pharmacological agents has expanded across multiple disciplines. This review mainly discusses their potential application in Alzheimer’s disease.
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作者：
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通讯作者：
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DOI：
10.1073/pnas.0700854104
发表时间：
2007-03-20
影响因子：
11.1
作者：
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通讯作者：
Goldman, Robert D.