2. Academic Validation
  3. Bifunctional Copper Chelators Capable of Reducing Aβ Aggregation and Aβ-Induced Oxidative Stress

Bifunctional Copper Chelators Capable of Reducing Aβ Aggregation and Aβ-Induced Oxidative Stress

  • ACS Omega. 2024 Oct 17;9(43):43376-43384. doi: 10.1021/acsomega.4c03152.
Olga Krasnovskaya 1,  Daniil Abramchuk 1,  Alexander Vaneev 1 2,  Petr Gorelkin 2,  Maxim Abakumov 2 3,  Roman Timoshenko 2,  Ilia Kuzmichev 4,  Nelly Chmelyuk 2,  Veronika Vadehina 3 4,  Regina Kuanaeva 2,  Evgeniy Dubrovin 2 5,  Vasilii Kolmogorov 2,  Elena Beloglazkina 1,  Olga Kechko 6,  Vladimir Mitkevich 6,  Kseniya Varshavskaya 6,  Sergey Salikhov 2,  Alexander Erofeev 1 2
Affiliations

Affiliations

  • 1 Chemistry Department, Lomonosov Moscow State University, Leninskie gory 1,3, Moscow 119991, Russia.
  • 2 National University of Science and Technology (MISIS), Leninskiy prospect 4, Moscow 119049, Russia.
  • 3 Pirogov Russian National Research Medical University (RNRMU), Moscow 117997, Russia.
  • 4 Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119991, Russia.
  • 5 Faculty of Physics, Lomonosov Moscow State University, Leninskie Gory 1, 2, Moscow 119991, Russia.
  • 6 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
PMID: 39493999 DOI: 10.1021/acsomega.4c03152
Abstract

Five bifunctional copper Chelating Agents, Alz-(1-5), designed to prevent beta-amyloid (Aβ) aggregation, were synthesized, and the leader compound (Alz-5) was chosen. Alz-5 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 Aβ42-affected human neuroblastoma SH-SY5Y cells revealed significant antioxidant activity of Alz-5. AFM data obtained on Aβ42 fibrils clearly indicate the antiaggregating property of Alz-5. To gain insights into the changes in the physiomechanical properties of Aβ42-affected cells, as well as in order to evaluate the antiaggregating ability of Alz-5, Young's modulus mapping on living SH-SY5Y cells affected consequently by Aβ42 and Alz-5 was conducted, and the ability of Alz-5 to decrease cell rigidity induced by Aβ42 was indisputably proven. Low cell toxicity and antioxidating properties, in conjunction with AFM and SICM-based biophysical provided on Aβ42-affected SH-SY5Y cells, support Alz-5 as a potential inhibitor of Aβ aggregation.

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