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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1501874

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

Provisionally accepted
Kseniya B. Varshavskaya Kseniya B. Varshavskaya 1Evgeny P. Barykin Evgeny P. Barykin 1Roman V. Timoshenko Roman V. Timoshenko 2Vasilii S. Kolmogorov Vasilii S. Kolmogorov 2,3Alexander S. Erofeev Alexander S. Erofeev 2Petr V. Gorelkin Petr V. Gorelkin 2Vladimir A. Mitkevich Vladimir A. Mitkevich 1*Alexander A. Makarov Alexander A. Makarov 1
  • 1 Engelhardt Institute of Molecular Biology (RAS), Moscow, Russia
  • 2 National University of Science and Technology MISiS, Moscow, Moscow Oblast, Russia
  • 3 Lomonosov Moscow State University, Moscow, Moscow, Russia

The final, formatted version of the article will be published soon.

    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-Aβ 42 ) and Asp7 isomerization (iso-Aβ 42 ) 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 Aβ 42 resulted in the largest increase in cell Young's modulus of all isoforms after 4 hours of incubation, while pS8-Aβ 42 induced the greatest increase in stiffness and ROS levels after 24 hours of incubation. Analysis of signaling proteins involved in the regulation of the actin cytoskeleton showed that Aβ 42 , pS8-Aβ 42 and iso-Aβ 42 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.

    Keywords: Alzheimer's disease, beta-amyloid, post-translational modifications, scanning ionconductance microscopy, ROS, Actin Cytoskeleton, cofilin, Protein Kinases

    Received: 25 Sep 2024; Accepted: 04 Nov 2024.

    Copyright: © 2024 Varshavskaya, Barykin, Timoshenko, Kolmogorov, Erofeev, Gorelkin, Mitkevich and Makarov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Vladimir A. Mitkevich, Engelhardt Institute of Molecular Biology (RAS), Moscow, Russia

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