Fluid levity of the cell: Role of membrane lipid architecture in genetic sphingolipidoses.
Fluid levity of the cell: Role of membrane lipid architecture in genetic sphingolipidoses.
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DOI：
10.1002/jnr.23750
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发表时间：
2016-11
影响因子：
4.2
通讯作者：
Bongarzone, Ernesto R.
中科院分区：
文献类型：
--
作者：
D'Auria, Ludovic;Bongarzone, Ernesto R.
鞘磷脂病是由于调节鞘脂代谢的关键酶的遗传性功能丧失，以及这些脂类在受影响的细胞中大量积累而引起的。最常见的毒性表现在神经系统，那里的神经元和胶质细胞的生存和功能受到最大的影响。虽然有关于疾病晚期神经胶质细胞变化的详细信息，但触发神经病理的最初致病机制在很大程度上尚不清楚。鞘磷脂作为生物膜的关键成分，其局部浓度的变化可能会影响膜结构域和功能的组织。本文认为，鞘磷脂的毒性包括脂域完整性、膜流动性和膜弯曲的初始缺陷，导致膜变形，以及细胞信号和功能的紊乱。了解鞘脂如何改变膜结构可能为更有效地治疗鞘脂病提供突破。鞘磷脂病是一种严重的不可治愈的神经系统疾病，鞘脂在未知的机制下积聚到高水平和有毒的水平。神经鞘磷脂在Krabbe病中可插入细胞膜，降低流动性，破坏功能脂域和/或引起膜曲率改变，导致膜脆性和细胞信号/功能紊乱。
Sphingolipidoses arise from inherited loss-of-function of key enzymes regulating the sphingolipid metabolism, and the accumulation of large quantities of these lipids in affected cells. Most frequently, toxicity is manifested in the nervous system, where survival and function of neurons and glial cells are most impacted. Although detailed information is available about neuroglial alterations during terminal stages of the disease, the initial pathogenic mechanisms triggering neuropathology are largely unclear. Being key components of biological membranes, changes in the local concentration of sphingolipids are likely to impact in the organization of membrane domains and functions. This essay proposes that sphingolipids' toxicity involves initial defects in the integrity of lipid domains, membrane fluidity, and membrane bending, leading to membrane deformation, and deregulation of cell signaling and function. Understanding how sphingolipids alter membrane architecture may provide breakthroughs for more efficient treatment of sphingolipidoses. Sphingolipidoses are severe and incurable neurological diseases, where sphingolipids accumulate to high and toxic levels by unknown mechanism. Sphingolipids such as psychosine in Krabbe disease could insert in membrane, decreasing fluidity and disrupting functional lipid domains and/or induce changes in membrane curvature, leading to membrane fragility and cell signaling/function deregulation.
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筏结构域的动态重新分布是细胞趋化过程中信号传导的组织平台。
影响因子：
7.8
作者：
Gómez-Moutón, C;Lacalle, RA;Mira, E;Jiménez-Baranda, S;Barber, DF;Carrera, AC;Martínez, C;Mañes, S
通讯作者：
Mañes, S
DOI：
10.1523/jneurosci.1243-10.2010
发表时间：
2010-09-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Jana A;Pahan K
通讯作者：
Pahan K
影响因子：
3.4
作者：
Dietrich, C;Bagatolli, LA;Gratton, E
通讯作者：
Gratton, E
影响因子：
6.1
作者：
Cantuti-Castelvetri, Ludovico;Zhu, Hongling;Givogri, Maria I.;Chidavaenzi, Robstein L.;Lopez-Rosas, Aurora;Bongarzone, Ernesto R.
通讯作者：
Bongarzone, Ernesto R.
影响因子：
64.5
作者：
Köberlin MS;Snijder B;Heinz LX;Baumann CL;Fauster A;Vladimer GI;Gavin AC;Superti-Furga G
通讯作者：
Superti-Furga G