Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral Nerves
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- Inflammation and dysregulation of the immune system are hallmarks of several neurodegenerative diseases. An activated immune response is considered to be the cause of myelin breakdown in demyelinating disorders. In the peripheral nervous system (PNS), myelin can be degraded in an autophagy-dependent manner directly by Schwann cells or by macrophages, which are modulated by T-lymphocytes. Here, we show that the NF-κB activator Pleckstrin homology containing family member 5 (Plekhg5) is involved in the regulation of both Schwann cell autophagyInflammation and dysregulation of the immune system are hallmarks of several neurodegenerative diseases. An activated immune response is considered to be the cause of myelin breakdown in demyelinating disorders. In the peripheral nervous system (PNS), myelin can be degraded in an autophagy-dependent manner directly by Schwann cells or by macrophages, which are modulated by T-lymphocytes. Here, we show that the NF-κB activator Pleckstrin homology containing family member 5 (Plekhg5) is involved in the regulation of both Schwann cell autophagy and recruitment of T-lymphocytes in peripheral nerves during motoneuron disease. Plekhg5-deficient mice show defective axon/Schwann cell units characterized by myelin infoldings in peripheral nerves. Even at late stages, Plekhg5-deficient mice do not show any signs of demyelination and inflammation. Using RNAseq, we identified a transcriptional signature for an impaired immune response in sciatic nerves, which manifested in a reduced number of CD4\(^+\) and CD8\(^+\) T-cells. These findings identify Plekhg5 as a promising target to impede myelin breakdown in demyelinating PNS disorders.…
Autor(en): | Patrick Lüningschrör, Carsten Slotta, Peter Heimann, Michael Briese, Ulrich M. Weikert, Bita Massih, Silke Appenzeller, Michael Sendtner, Christian Kaltschmidt, Barbara Kaltschmidt |
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URN: | urn:nbn:de:bvb:20-opus-207538 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Klinische Neurobiologie |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Frontiers in Cellular Neuroscience |
ISSN: | 1662-5102 |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 14 |
Aufsatznummer: | 185 |
Originalveröffentlichung / Quelle: | Frontiers in Cellular Neuroscience 2020, 14:185. doi: 10.3389/fncel.2020.00185 |
DOI: | https://doi.org/10.3389/fncel.2020.00185 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | PLEKHG5; Schwann cells; autophagy; immune response; myelin |
Datum der Freischaltung: | 04.03.2021 |
Datum der Erstveröffentlichung: | 07.07.2020 |
Open-Access-Publikationsfonds / Förderzeitraum 2020 | |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |