TY  - JOUR
A1  - Lüningschrör, Patrick
A1  - Slotta, Carsten
A1  - Heimann, Peter
A1  - Briese, Michael
A1  - Weikert, Ulrich M.
A1  - Massih, Bita
A1  - Appenzeller, Silke
A1  - Sendtner, Michael
A1  - Kaltschmidt, Christian
A1  - Kaltschmidt, Barbara
T1  - Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral Nerves
T2  - Frontiers in Cellular Neuroscience
N2  - 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 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.
KW  - Schwann cells
KW  - autophagy
KW  - immune response
KW  - myelin
KW  - PLEKHG5
Y1  - 2020
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/20753
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-207538
SN  - 1662-5102
VL  - 14
ER  -