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

Autor: Komleva YK; Department of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry, Krasnoyarsk State Medical University Named after Prof. V.F. Voino-Yasenetsky, 660022 Krasnoyarsk, Russia.; Research Institute of Molecular Medicine and Pathobiochemistry, 660022 Krasnoyarsk, Russia., Potapenko IV; Research Institute of Molecular Medicine and Pathobiochemistry, 660022 Krasnoyarsk, Russia., Lopatina OL; Department of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry, Krasnoyarsk State Medical University Named after Prof. V.F. Voino-Yasenetsky, 660022 Krasnoyarsk, Russia.; Shared Research Center for Molecular and Cellular Technologies, 660022 Krasnoyarsk, Russia., Gorina YV; Department of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry, Krasnoyarsk State Medical University Named after Prof. V.F. Voino-Yasenetsky, 660022 Krasnoyarsk, Russia.; Research Institute of Molecular Medicine and Pathobiochemistry, 660022 Krasnoyarsk, Russia., Chernykh A; Research Institute of Molecular Medicine and Pathobiochemistry, 660022 Krasnoyarsk, Russia., Khilazheva ED; Department of Biochemistry, Medical, Pharmaceutical & Toxicological Chemistry, Krasnoyarsk State Medical University Named after Prof. V.F. Voino-Yasenetsky, 660022 Krasnoyarsk, Russia.; Research Institute of Molecular Medicine and Pathobiochemistry, 660022 Krasnoyarsk, Russia., Salmina AB; Research Institute of Molecular Medicine and Pathobiochemistry, 660022 Krasnoyarsk, Russia.; Laboratory of Experimental Brain Cytology, Division of Brain Sciences, Research Center of Neurology, 125367 Moscow, Russia., Shuvaev AN; Research Institute of Molecular Medicine and Pathobiochemistry, 660022 Krasnoyarsk, Russia.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2021 Oct 27; Vol. 22 (21). Date of Electronic Publication: 2021 Oct 27.
DOI: 10.3390/ijms222111588
Abstrakt: 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.
Databáze: MEDLINE
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