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
JF  - 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
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207538
SN  - 1662-5102
VL  - 14
ER  - 
TY  - JOUR
A1  - Thangaraj Selvaraj, Bhuvaneish
A1  - Frank, Nicolas
A1  - Bender, Florian L. P.
A1  - Asan, Esther
A1  - Sendtner, Michael
T1  - Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease
JF  - The Journal of Cell Biology
N2  - Axonal maintenance, plasticity, and regeneration are influenced by signals from neighboring cells, in particular Schwann cells of the peripheral nervous system. Schwann cells produce neurotrophic factors, but the mechanisms by which ciliary neurotrophic factor (CNTF) and other neurotrophic molecules modify the axonal cytoskeleton are not well understood. In this paper, we show that activated signal transducer and activator of transcription-3 (STAT3), an intracellular mediator of the effects of CNTF and other neurotrophic cytokines, acts locally in axons of motoneurons to modify the tubulin cytoskeleton. Specifically, we show that activated STAT3 interacted with stathmin and inhibited its microtubule-destabilizing activity. Thus, ectopic CNTF-mediated activation of STAT3 restored axon elongation and maintenance in motoneurons from progressive motor neuronopathy mutant mice, a mouse model of motoneuron disease. This mechanism could also be relevant for other neurodegenerative diseases and provide a target for new therapies for axonal degeneration.
KW  - Schwann cells
KW  - transcription-3 (STAT3)
KW  - ciliary neurotrophic factor (CNTF)
KW  - axonal degeneration
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154675
VL  - 199
IS  - 3
SP  - 437
EP  - 451
ER  -