Indolylazine Derivative Induces Chaperone Expression in Aged Neural Cells and Prevents the Progression of Alzheimer’s Disease
Электронный научный архив УРФУ
Информация об архиве | Просмотр оригинала| Поле | Значение | |
| Заглавие |
Indolylazine Derivative Induces Chaperone Expression in Aged Neural Cells and Prevents the Progression of Alzheimer’s Disease
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| Автор |
Lazarev, V. F.
Dutysheva, E. A. Mikhaylova, E. R. Trestsova, M. A. Utepova, I. A. Chupakhin, O. N. Margulis, B. A. Guzhova, I. V. |
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| Тематика |
AGEING
ALZHEIMER’S DISEASE CELLULAR PROTEOSTASIS IA-50 MOLECULAR CHAPERONES AGING ALZHEIMER DISEASE AMYLOID BETA-PEPTIDES ANIMALS DISEASE MODELS, ANIMAL MICE MICE, TRANSGENIC MOLECULAR CHAPERONES NEURONS AMYLOID BETA PROTEIN CHAPERONE AGING ALZHEIMER DISEASE ANIMAL DISEASE MODEL METABOLISM MOUSE NERVE CELL TRANSGENIC MOUSE |
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| Описание |
The risk of progression of most sporadic neurodegenerative diseases, including Alzheimer’s disease, increases with age. Traditionally, this is associated with a decrease in the efficiency of cell protection systems, in particular, molecular chaperones. Thus, the development of small molecules able to induce the synthesis of chaperones is a promising therapeutic approach to prevent neural diseases associated with ageing. Here, we describe a new compound IA-50, belonging to the class of indolylazines and featured by a low size of topological polar surface area, the property related to substances with potentially high membrane-penetrating activity. We also estimated the absorption, distribution, metabolism and excretion characteristics of IA-50 and found the substance to fit the effective drug criteria. The new compound was found to induce the synthesis and accumulation of Hsp70 in normal and aged neurons and in the hippocampi of young and old mice. The transgenic model of Alzheimer’s disease, based on 5xFAD mice, confirmed that the injection of IA-50 prevented the formation of β-amyloid aggregates, loss of hippocampal neurons and the development of memory impairment. These data indicate that this novel substance may induce the expression of chaperones in neural cells and brain tissues, suggesting its possible application in the therapy of ageing-associated disorders. © 2022 by the authors.
Ministry of Education and Science of the Russian Federation, Minobrnauka, (075-15-2021-683) Ministry of Science and Higher Education of the Russian Federation, (13.1902.21.0027, N 075-15-2020-795) Funding text 1: For further verification of the chaperone-inducing and neuroprotective properties of PLAs, we used mesenchymal stem cells from Wharton’s jelly of human umbilical cord (MSCWJ-2) cells that was described earlier []. The cells were received from the shared research facility “Vertebrate cell culture collection” supported by the Ministry of Science and Higher Education of the Russian Federation (Agreement NO. 075-15-2021-683). Cells were cultured in DMEM/F12 medium (Gibco, Paisley, UK), containing 10% fetal bovine serum (FBS Gibco, Paisley, UK), 100 units/mL penicillin and 0.1 mg/mL streptomycin (BioloT, St.Petersburg, Russia) at 37 °C and 5% CO. We reprogrammed these cells into a neuronal phenotype for 5 days in a Neurobasal medium (Gibco, Paisley, UK), containing B27 supplement (Gibco, Paisley, UK), 3% FBS, 100 units/mL penicillin and 0.1 mg/mL streptomycin. Verification of the neuronal phenotype was carried out based on the analysis of the expression of neuronal markers MAP-2 and β-3-tubulin, using a real-time polymerase chain reaction. The cells were named MSCWJ-NEU. 2 Funding text 2: The research was supported by the Ministry of Science and Higher Education of Russia, Research Project N 075-15-2020-795, local identifier 13.1902.21.0027. |
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| Дата |
2024-04-08T11:06:40Z
2024-04-08T11:06:40Z 2022 |
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| Тип |
Article
Journal article (info:eu-repo/semantics/article) Published version (info:eu-repo/semantics/publishedVersion) |
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| Идентификатор |
Lazarev, VF, Dutysheva, EA, Mikhaylova, ER, Trestsova, MA, Utepova, IA, Chupakhin, ON, Margulis, BA & Guzhova, IV 2022, 'Indolylazine Derivative Induces Chaperone Expression in Aged Neural Cells and Prevents the Progression of Alzheimer’s Disease', Molecules, Том. 27, № 24, 8950. https://doi.org/10.3390/molecules27248950
Lazarev, V. F., Dutysheva, E. A., Mikhaylova, E. R., Trestsova, M. A., Utepova, I. A., Chupakhin, O. N., Margulis, B. A., & Guzhova, I. V. (2022). Indolylazine Derivative Induces Chaperone Expression in Aged Neural Cells and Prevents the Progression of Alzheimer’s Disease. Molecules, 27(24), [8950]. https://doi.org/10.3390/molecules27248950 1420-3049 Final All Open Access; Gold Open Access; Green Open Access https://www.mdpi.com/1420-3049/27/24/8950/pdf?version=1671523175 https://www.mdpi.com/1420-3049/27/24/8950/pdf?version=1671523175 http://elar.urfu.ru/handle/10995/131333 10.3390/molecules27248950 85144487563 000902708000001 |
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en
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| Права |
Open access (info:eu-repo/semantics/openAccess)
cc-by https://creativecommons.org/licenses/by/4.0/ |
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application/pdf
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MDPI
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| Источник |
Molecules
Molecules |
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