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脂质作为感觉 TRP 通道的中枢调节剂。

Lipids as central modulators of sensory TRP channels.

机构信息

DIMES Sezione Fisiologia Umana, Viale Benedetto XV n 3, 16132 Genova, Italy.

Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Av. De la Universidad s/n, Elche, Spain.

出版信息

Biochim Biophys Acta Biomembr. 2017 Sep;1859(9 Pt B):1615-1628. doi: 10.1016/j.bbamem.2017.04.012. Epub 2017 Apr 18.

Abstract

The transient receptor potential (TRP) ion channel family is involved in a diversity of physiological processes including sensory and homeostatic functions, as well as muscle contraction and vasomotor control. Their dysfunction contributes to the etiology of several diseases, being validated as therapeutic targets. These ion channels may be activated by physical or chemical stimuli and their function is highly influenced by signaling molecules activated by extracellular signals. Notably, as integral membrane proteins, lipid molecules also modulate their membrane location and function either by direct interaction with the channel structure or by modulating the physico-chemical properties of the cellular membrane. This lipid-based modulatory effect is being considered an alternative and promising approach to regulate TRP channel dysfunction in diseases. Here, we review the current progress in this exciting field highlighting a complex channel regulation by a large diversity of lipid molecules and suggesting some diseases that may benefit from a membrane lipid therapy. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

摘要

瞬时受体电位 (TRP) 离子通道家族参与多种生理过程,包括感觉和体内平衡功能,以及肌肉收缩和血管运动控制。它们的功能障碍导致了多种疾病的发生,因此被验证为治疗靶点。这些离子通道可以被物理或化学刺激激活,其功能受到细胞外信号激活的信号分子的高度影响。值得注意的是,作为整合膜蛋白,脂质分子也可以通过与通道结构的直接相互作用或通过调节细胞膜的物理化学性质来调节其膜位置和功能。这种基于脂质的调节作用被认为是一种替代的、有前途的方法,可以调节疾病中 TRP 通道的功能障碍。在这里,我们回顾了这一令人兴奋的领域的最新进展,强调了大量不同的脂质分子对通道的复杂调节,并提出了一些可能受益于膜脂治疗的疾病。本文是由 Pablo V. Escribá 编辑的题为“膜脂治疗:靶向生物膜的药物”的特刊的一部分。

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