دورية أكاديمية

Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome

التفاصيل البيبلوغرافية
العنوان: Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain–Barre Syndrome
المؤلفون: Verica Paunovic, Stojan Peric, Irena Vukovic, Marina Stamenkovic, Emina Milosevic, Danijela Stevanovic, Milos Mandic, Ivana Basta, Ivana Berisavac, Mirjana Arsenijevic, Ivo Bozovic, Marko Nikolic, Zorica Stevic, Vladimir Trajkovic
المصدر: Cells; Volume 11; Issue 18; Pages: 2897
بيانات النشر: Multidisciplinary Digital Publishing Institute
سنة النشر: 2022
المجموعة: MDPI Open Access Publishing
مصطلحات موضوعية: Guillain–Barré syndrome, peripheral blood mononuclear cells, AMP-activated protein kinase, autophagy, mTOR, metformin
الوصف: 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.
نوع الوثيقة: text
وصف الملف: application/pdf
اللغة: English
العلاقة: Autophagy; https://dx.doi.org/10.3390/cells11182897Test
DOI: 10.3390/cells11182897
الإتاحة: https://doi.org/10.3390/cells11182897Test
حقوق: https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.DFA4568C
قاعدة البيانات: BASE