Effect of Amyloid-β Monomers on Lipid Membrane Mechanical Parameters-Potential Implications for Mechanically Driven Neurodegeneration in Alzheimer's Disease.
Effect of Amyloid-β Monomers on Lipid Membrane Mechanical Parameters-Potential Implications for Mechanically Driven Neurodegeneration in Alzheimer's Disease.
复制标题
淀粉样蛋白-β单体对脂膜机械参数的影响--阿尔茨海默病中机械驱动的神经变性的潜在含义。
DOI：
10.3390/ijms22010018
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发表时间：
2020-12-22
影响因子：
5.6
通讯作者：
Kraszewski S
中科院分区：
文献类型：
--
作者：
Drabik D;Chodaczek G;Kraszewski S
阿尔茨海默病(AD)是一种神经退行性疾病，会导致记忆丧失和认知技能障碍。AD的发病机制有多种，如淀粉样蛋白(Aβ，Aβ)进行性积聚和τ病理。然而，Aβ的确切神经退变机制仍然很复杂，还不完全清楚。本文提出了一种基于维持神经细胞膜机械平衡的机制的替代假说。A-β的引入降低了脂膜的弹性，最终导致膜团的破坏、机械波的传播中断和伽马振荡的改变。前两种会破坏神经元正常运作的能力，而后一种则会降低感觉编码和感知能力。为了开始讨论这个机械平衡假说，我们测量了两个选定的多肽，Aβ-40和Aβ-42，以及它们的荧光标记修饰对膜机械性能的影响。通过分子动力学研究和实验闪烁噪声技术观察到弯曲刚性的降低，这与所有被研究的多肽一致。此外，用分子动力学研究了有或没有掺入神经退行性变多肽的膜中波的传播。在加入A-β的膜体系中，膜的行为发生了变化。
Alzheimer’s disease (AD) is a neurodegenerative disease that results in memory loss and the impairment of cognitive skills. Several mechanisms of AD’s pathogenesis were proposed, such as the progressive accumulation of amyloid-β (Aβ) and τ pathology. Nevertheless, the exact neurodegenerative mechanism of the Aβ remains complex and not fully understood. This paper proposes an alternative hypothesis of the mechanism based on maintaining the neuron membrane’s mechanical balance. The incorporation of Aβ decreases the lipid membrane’s elastic properties, which eventually leads to the impairment of membrane clustering, disruption of mechanical wave propagation, and change in gamma oscillations. The first two disrupt the neuron’s ability to function correctly while the last one decreases sensory encoding and perception enabling. To begin discussing this mechanical-balance hypothesis, we measured the effect of two selected peptides, Aβ-40 and Aβ-42, as well as their fluorescently labeled modification, on membrane mechanical properties. The decrease of bending rigidity, consistent for all investigated peptides, was observed using molecular dynamic studies and experimental flicker-noise techniques. Additionally, wave propagation was investigated with molecular dynamic studies in membranes with and without incorporated neurodegenerative peptides. A change in membrane behavior was observed in the membrane system with incorporated Aβ.
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影响因子：
4
作者：
Hicks DA;Nalivaeva NN;Turner AJ
通讯作者：
Turner AJ
影响因子：
3.4
作者：
Koshiyama, Kenichiro;Kodama, Tetsuya;Fujikawa, Shigeo
通讯作者：
Fujikawa, Shigeo
影响因子：
4.7
作者：
Barz, Helmut;Schreiber, Almut;Barz, Ulrich
通讯作者：
Barz, Ulrich
影响因子：
3.9
作者：
Drabik, Dominik;Chodaczek, Grzegorz;Langner, Marek
通讯作者：
Langner, Marek
DOI：
10.1007/978-0-387-76715-4_11
发表时间：
2007-01-01
期刊：
AXON GROWTH AND GUIDANCE
影响因子：
--
作者：
Guirland, Carmine;Zheng, James Q.
通讯作者：
Zheng, James Q.