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Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome
AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin (mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signa...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496801/ https://www.ncbi.nlm.nih.gov/pubmed/36139470 http://dx.doi.org/10.3390/cells11182897 |
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author | Paunovic, Verica Peric, Stojan Vukovic, Irena Stamenkovic, Marina Milosevic, Emina Stevanovic, Danijela Mandic, Milos Basta, Ivana Berisavac, Ivana Arsenijevic, Mirjana Bozovic, Ivo Nikolic, Marko Stevic, Zorica Trajkovic, Vladimir |
author_facet | Paunovic, Verica Peric, Stojan Vukovic, Irena Stamenkovic, Marina Milosevic, Emina Stevanovic, Danijela Mandic, Milos Basta, Ivana Berisavac, Ivana Arsenijevic, Mirjana Bozovic, Ivo Nikolic, Marko Stevic, Zorica Trajkovic, Vladimir |
author_sort | Paunovic, Verica |
collection | PubMed |
description | AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin (mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signaling pathway and autophagy markers were analyzed by immunoblotting in blood mononuclear cells of 20 healthy control subjects and 23 patients with an acute demyelinating form of Guillain–Barré syndrome (GBS). The activation of the liver kinase B1 (LKB1)/AMPK/Raptor signaling axis was significantly reduced in GBS compared to control subjects. In contrast, the phosphorylated forms of mTOR activator AKT and mTOR substrate 4EBP1, as well as the levels of autophagy markers LC3-II, beclin-1, ATG5, p62/sequestosome 1, and NBR1 were similar between the two groups. The downregulation of LKB1/AMPK signaling, but not the activation status of the AKT/mTOR/4EBP1 pathway or the levels of autophagy markers, correlated with higher clinical activity and worse outcomes of GBS. A retrospective study in a diabetic cohort of GBS patients demonstrated that treatment with AMPK activator metformin was associated with milder GBS compared to insulin/sulphonylurea therapy. In conclusion, the impairment of the LKB1/AMPK pathway might contribute to the development/progression of GBS, thus representing a potential therapeutic target in this immune-mediated peripheral polyneuropathy. |
format | Online Article Text |
id | pubmed-9496801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94968012022-09-23 Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome Paunovic, Verica Peric, Stojan Vukovic, Irena Stamenkovic, Marina Milosevic, Emina Stevanovic, Danijela Mandic, Milos Basta, Ivana Berisavac, Ivana Arsenijevic, Mirjana Bozovic, Ivo Nikolic, Marko Stevic, Zorica Trajkovic, Vladimir Cells Article AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin (mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signaling pathway and autophagy markers were analyzed by immunoblotting in blood mononuclear cells of 20 healthy control subjects and 23 patients with an acute demyelinating form of Guillain–Barré syndrome (GBS). The activation of the liver kinase B1 (LKB1)/AMPK/Raptor signaling axis was significantly reduced in GBS compared to control subjects. In contrast, the phosphorylated forms of mTOR activator AKT and mTOR substrate 4EBP1, as well as the levels of autophagy markers LC3-II, beclin-1, ATG5, p62/sequestosome 1, and NBR1 were similar between the two groups. The downregulation of LKB1/AMPK signaling, but not the activation status of the AKT/mTOR/4EBP1 pathway or the levels of autophagy markers, correlated with higher clinical activity and worse outcomes of GBS. A retrospective study in a diabetic cohort of GBS patients demonstrated that treatment with AMPK activator metformin was associated with milder GBS compared to insulin/sulphonylurea therapy. In conclusion, the impairment of the LKB1/AMPK pathway might contribute to the development/progression of GBS, thus representing a potential therapeutic target in this immune-mediated peripheral polyneuropathy. MDPI 2022-09-16 /pmc/articles/PMC9496801/ /pubmed/36139470 http://dx.doi.org/10.3390/cells11182897 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Paunovic, Verica Peric, Stojan Vukovic, Irena Stamenkovic, Marina Milosevic, Emina Stevanovic, Danijela Mandic, Milos Basta, Ivana Berisavac, Ivana Arsenijevic, Mirjana Bozovic, Ivo Nikolic, Marko Stevic, Zorica Trajkovic, Vladimir Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome |
title | Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome |
title_full | Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome |
title_fullStr | Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome |
title_full_unstemmed | Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome |
title_short | Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome |
title_sort | downregulation of lkb1/ampk signaling in blood mononuclear cells is associated with the severity of guillain–barre syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496801/ https://www.ncbi.nlm.nih.gov/pubmed/36139470 http://dx.doi.org/10.3390/cells11182897 |
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