NLRP3 Inflammasome Blocking as a Potential Treatment of Central Insulin Resistance in Early-Stage Alzheimer’s Disease

Background: Alzheimer’s disease (AD) is a devastating neurodegenerative disorder. In recent years, attention of researchers has increasingly been focused on studying the role of brain insulin resistance (BIR) in the AD pathogenesis. Neuroinflammation makes a significant contribution to the BIR due t...

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Autores principales:	Yulia K. Komleva, Ilia V. Potapenko, Olga L. Lopatina, Yana V. Gorina, Anatoly Chernykh, Elena D. Khilazheva, Alla B. Salmina, Anton N. Shuvaev
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Alzheimer’s disease neuroinflammation brain insulin resistance NLRP3 inflammasome cognitive disorders Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/7f90f583e625413fa6044b88b1ccddcd
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spelling	oai:doaj.org-article:7f90f583e625413fa6044b88b1ccddcd2021-11-11T17:04:13ZNLRP3 Inflammasome Blocking as a Potential Treatment of Central Insulin Resistance in Early-Stage Alzheimer’s Disease10.3390/ijms2221115881422-00671661-6596https://doaj.org/article/7f90f583e625413fa6044b88b1ccddcd2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11588https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Background: Alzheimer’s disease (AD) is a devastating neurodegenerative disorder. In recent years, attention of researchers has increasingly been focused on studying the role of brain insulin resistance (BIR) in the AD pathogenesis. Neuroinflammation makes a significant contribution to the BIR due to the activation of NLRP3 inflammasome. This study was devoted to the understanding of the potential therapeutic roles of the NLRP3 inflammasome in neurodegeneration occurring concomitant with BIR and its contribution to the progression of emotional disorders. Methods: To test the impact of innate immune signaling on the changes induced by Aβ1-42 injection, we analyzed animals carrying a genetic deletion of the Nlrp3 gene. Thus, we studied the role of NLRP3 inflammasomes in health and neurodegeneration in maintaining brain insulin signaling using behavioral, electrophysiological approaches, immunohistochemistry, ELISA and real-time PCR. Results: We revealed that NLRP3 inflammasomes are required for insulin-dependent glucose transport in the brain and memory consolidation. Conclusions NLRP3 knockout protects mice against the development of BIR: Taken together, our data reveal the protective role of Nlrp3 deletion in the regulation of fear memory and the development of Aβ-induced insulin resistance, providing a novel target for the clinical treatment of this disorder.Yulia K. KomlevaIlia V. PotapenkoOlga L. LopatinaYana V. GorinaAnatoly ChernykhElena D. KhilazhevaAlla B. SalminaAnton N. ShuvaevMDPI AGarticleAlzheimer’s diseaseneuroinflammationbrain insulin resistanceNLRP3 inflammasomecognitive disordersBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11588, p 11588 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease neuroinflammation brain insulin resistance NLRP3 inflammasome cognitive disorders Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Alzheimer’s disease neuroinflammation brain insulin resistance NLRP3 inflammasome cognitive disorders Biology (General) QH301-705.5 Chemistry QD1-999 Yulia K. Komleva Ilia V. Potapenko Olga L. Lopatina Yana V. Gorina Anatoly Chernykh Elena D. Khilazheva Alla B. Salmina Anton N. Shuvaev NLRP3 Inflammasome Blocking as a Potential Treatment of Central Insulin Resistance in Early-Stage Alzheimer’s Disease
description	Background: Alzheimer’s disease (AD) is a devastating neurodegenerative disorder. In recent years, attention of researchers has increasingly been focused on studying the role of brain insulin resistance (BIR) in the AD pathogenesis. Neuroinflammation makes a significant contribution to the BIR due to the activation of NLRP3 inflammasome. This study was devoted to the understanding of the potential therapeutic roles of the NLRP3 inflammasome in neurodegeneration occurring concomitant with BIR and its contribution to the progression of emotional disorders. Methods: To test the impact of innate immune signaling on the changes induced by Aβ1-42 injection, we analyzed animals carrying a genetic deletion of the Nlrp3 gene. Thus, we studied the role of NLRP3 inflammasomes in health and neurodegeneration in maintaining brain insulin signaling using behavioral, electrophysiological approaches, immunohistochemistry, ELISA and real-time PCR. Results: We revealed that NLRP3 inflammasomes are required for insulin-dependent glucose transport in the brain and memory consolidation. Conclusions NLRP3 knockout protects mice against the development of BIR: Taken together, our data reveal the protective role of Nlrp3 deletion in the regulation of fear memory and the development of Aβ-induced insulin resistance, providing a novel target for the clinical treatment of this disorder.
format	article
author	Yulia K. Komleva Ilia V. Potapenko Olga L. Lopatina Yana V. Gorina Anatoly Chernykh Elena D. Khilazheva Alla B. Salmina Anton N. Shuvaev
author_facet	Yulia K. Komleva Ilia V. Potapenko Olga L. Lopatina Yana V. Gorina Anatoly Chernykh Elena D. Khilazheva Alla B. Salmina Anton N. Shuvaev
author_sort	Yulia K. Komleva
title	NLRP3 Inflammasome Blocking as a Potential Treatment of Central Insulin Resistance in Early-Stage Alzheimer’s Disease
title_short	NLRP3 Inflammasome Blocking as a Potential Treatment of Central Insulin Resistance in Early-Stage Alzheimer’s Disease
title_full	NLRP3 Inflammasome Blocking as a Potential Treatment of Central Insulin Resistance in Early-Stage Alzheimer’s Disease
title_fullStr	NLRP3 Inflammasome Blocking as a Potential Treatment of Central Insulin Resistance in Early-Stage Alzheimer’s Disease
title_full_unstemmed	NLRP3 Inflammasome Blocking as a Potential Treatment of Central Insulin Resistance in Early-Stage Alzheimer’s Disease
title_sort	nlrp3 inflammasome blocking as a potential treatment of central insulin resistance in early-stage alzheimer’s disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7f90f583e625413fa6044b88b1ccddcd
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NLRP3 Inflammasome Blocking as a Potential Treatment of Central Insulin Resistance in Early-Stage Alzheimer’s Disease

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