Bifunctional Copper Chelators Capable of Reducing Aβ Aggregation and Aβ-Induced Oxidative Stress
Five bifunctional copper chelating agents, <b>Alz-(1-5)</b>, designed to prevent beta-amyloid (Aβ) aggregation, were synthesized, and the leader compound (<b>Alz-5</b>) was chosen. <b>Alz-5</b> acts as a bifunctional chelator that can interact with various Aβ aggregates and reduce their neurotoxicity. Reactive oxygen species measurements provided by the Pt-nanoelectrode technique in single Aβ<sub>42</sub>-affected human neuroblastoma SH-SY5Y cells revealed significant antioxidant activity of <b>Alz-5</b>. AFM data obtained on Aβ<sub>42</sub> fibrils clearly indicate the antiaggregating property of <b>Alz-5</b>. To gain insights into the changes in the physiomechanical properties of Aβ<sub>42</sub>-affected cells, as well as in order to evaluate the antiaggregating ability of <b>Alz-5</b>, Young's modulus mapping on living SH-SY5Y cells affected consequently by Aβ<sub>42</sub> and <b>Alz-5</b> was conducted, and the ability of <b>Alz-5</b> to decrease cell rigidity induced by Aβ<sub>42</sub> was indisputably proven. Low cell toxicity and antioxidating properties, in conjunction with AFM and SICM-based biophysical provided on Aβ<sub>42</sub>-affected SH-SY5Y cells, support <b>Alz-</b>5 as a potential inhibitor of Aβ aggregation.
Authors
- Vladimir A. Mitkevich (ORCID: https://orcid.org/0000-0002-1517-1983)
- Maxim A. Abakumov (ORCID: https://orcid.org/0000-0003-2622-9201)
- Nelly S. Chmelyuk (ORCID: https://orcid.org/0000-0002-2434-2465)
- Alexander N. Vaneev (ORCID: https://orcid.org/0000-0001-8201-8498)
- Alexander S. Erofeev (ORCID: https://orcid.org/0000-0002-6631-821X)
- Kseniya B. Varshavskaya
- Elena Kimovna Beloglazkina (ORCID: https://orcid.org/0000-0001-6796-8241)
- Evgeniy V. Dubrovin (ORCID: https://orcid.org/0000-0001-8883-5966)
- Daniil Abramchuk (ORCID: https://orcid.org/0009-0000-3664-2978)
- Василий Колмогоров (ORCID: https://orcid.org/0000-0002-7135-8910)
- S. V. Salikhov (ORCID: https://orcid.org/0000-0003-3202-7294)
- Olga Olegovna Krasnovskaya (ORCID: https://orcid.org/0000-0002-4948-2747)
- Roman V. Timoshenko (ORCID: https://orcid.org/0009-0007-6459-6455)
- Petr V. Gorelkin (ORCID: https://orcid.org/0000-0002-4860-9013)
- Regina Kuanaeva (ORCID: https://orcid.org/0009-0003-1948-7381)
- Ilia Kuzmichev
- Olga I. Kechko
- Veronika Vadehina
Institutions
- Engelhardt Institute of Molecular Biology (RU)
- National University of Science and Technology (RU)
- Russian Academy of Sciences (RU)
- Lomonosov Moscow State University (RU)
- Pirogov Russian National Research Medical University (RU)
- Federal Medical Research Centre for Psychiatry and Narcology (RU)
Publication Details
- Journal
- ACS Omega
- Published
- 2024-10-17
- DOI
- https://doi.org/10.1021/acsomega.4c03152
- Citations
- 5
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.63
Funders
- Ministry of Education and Science of the Russian Federation
- Ministry of Science and Higher Education of the Russian Federation