Post-translational modifications of beta-amyloid modulate its effect on cell mechanical properties and influence cytoskeletal signaling cascades.

IF 3.5 3区医学 Q2 NEUROSCIENCES Frontiers in Molecular Neuroscience Pub Date : 2024-11-14 eCollection Date: 2024-01-01 DOI:10.3389/fnmol.2024.1501874

Kseniya B Varshavskaya, Evgeny P Barykin, Roman V Timoshenko, Vasilii S Kolmogorov, Alexander S Erofeev, Petr V Gorelkin, Vladimir A Mitkevich, Alexander A Makarov

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引用次数: 0

Abstract

Post-translational modifications of beta-amyloid (Aβ) play an important role in the pathogenesis of Alzheimer's disease (AD). Aβ modifications such as Ser8 phosphorylation (pS8-Aβ₄₂) and Asp7 isomerization (iso-Aβ₄₂) can significantly alter the properties of Aβ and have been detected in vivo. One of the reasons for the different pathogenicity of Aβ isoforms may be the activation of different signaling cascades leading to changes in the mechanical properties of cells. In this paper, we used correlative scanning ion-conductance microscopy (SICM) and Pt-nanoelectrodes to compare the effects of Aβ isoforms on the Young's modulus of SH-SY5Y cells and the level of ROS. It was found that unmodified Aβ₄₂ resulted in the largest increase in cell Young's modulus of all isoforms after 4 h of incubation, while pS8-Aβ₄₂ induced the greatest increase in stiffness and ROS levels after 24 h of incubation. Analysis of signaling proteins involved in the regulation of the actin cytoskeleton showed that Aβ₄₂, pS8-Aβ₄₂ and iso-Aβ₄₂ have different effects on cofilin, GSK3β, LIMK, ERK and p38. This indicates that post-translational modifications of Aβ modulate its effect on neuronal cells through the activation of various signaling cascades, which affects the mechanical properties of cells.

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来源期刊

Frontiers in Molecular Neuroscience NEUROSCIENCES-

CiteScore

5.70

自引率

2.10%

发文量

669

审稿时长

14 weeks

期刊介绍： Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.