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Indolylazine Derivative Induces Chaperone Expression in Aged Neural Cells and Prevents the Progression of Alzheimer’s Disease. / Lazarev, Vladimir F.; Dutysheva, Elizaveta A.; Mikhaylova, Elena R. et al.
In: Molecules, Vol. 27, No. 24, 8950, 2022.

Research output: Contribution to journal › Article › peer-review

Harvard

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, vol. 27, no. 24, 8950. https://doi.org/10.3390/molecules27248950

APA

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

Vancouver

Lazarev VF, Dutysheva EA, Mikhaylova ER, Trestsova MA, Utepova IA, Chupakhin ON et al. Indolylazine Derivative Induces Chaperone Expression in Aged Neural Cells and Prevents the Progression of Alzheimer’s Disease. Molecules. 2022;27(24):8950. doi: 10.3390/molecules27248950

Author

Lazarev, Vladimir F. ; Dutysheva, Elizaveta A. ; Mikhaylova, Elena R. et al. / Indolylazine Derivative Induces Chaperone Expression in Aged Neural Cells and Prevents the Progression of Alzheimer’s Disease. In: Molecules. 2022 ; Vol. 27, No. 24.

BibTeX

@article{73194c13cf6f46ba846ff12cc03270c6,
title = "Indolylazine Derivative Induces Chaperone Expression in Aged Neural Cells and Prevents the Progression of Alzheimer{\textquoteright}s Disease",
abstract = "The risk of progression of most sporadic neurodegenerative diseases, including Alzheimer{\textquoteright}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{\textquoteright}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.",
author = "Lazarev, {Vladimir F.} and Dutysheva, {Elizaveta A.} and Mikhaylova, {Elena R.} and Trestsova, {Maria A.} and Utepova, {Irina A.} and Chupakhin, {Oleg N.} and Margulis, {Boris A.} and Guzhova, {Irina V.}",
note = "Текст о финансировании #1 For further verification of the chaperone-inducing and neuroprotective properties of PLAs, we used mesenchymal stem cells from Wharton{\textquoteright}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 Текст о финансировании #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.",
year = "2022",
doi = "10.3390/molecules27248950",
language = "English",
volume = "27",
journal = "Molecules",
issn = "1420-3049",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "24",

}

RIS

TY - JOUR

T1 - Indolylazine Derivative Induces Chaperone Expression in Aged Neural Cells and Prevents the Progression of Alzheimer’s Disease

AU - Lazarev, Vladimir F.

AU - Dutysheva, Elizaveta A.

AU - Mikhaylova, Elena R.

AU - Trestsova, Maria A.

AU - Utepova, Irina A.

AU - Chupakhin, Oleg N.

AU - Margulis, Boris A.

AU - Guzhova, Irina V.

N1 - Текст о финансировании #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 Текст о финансировании #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.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?partnerID=8YFLogxK&scp=85144487563

UR - https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=tsmetrics&SrcApp=tsm_test&DestApp=WOS_CPL&DestLinkType=FullRecord&KeyUT=000902708000001

U2 - 10.3390/molecules27248950

DO - 10.3390/molecules27248950

M3 - Article

VL - 27

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 24

M1 - 8950

ER -

ID: 33230040