Interplay between pro-inflammatory cytokines and chromatin-remodeling enzymes in the regulation of central nervous system demyelination and repair

A03

Our work suggests that modulating the activity of the enzyme HDAC1/2 could have multiple beneficial effects in the context of MS by decreasing demyelination induced by interleukin (IL-)17 and tumor necrosis factor (TNF), as well as by enhancing the remyelination of lesions. Here we want to study the role of HDAC1/2 and IL-17/TNF signaling and their interplay on myelination and remyelination of the CNS in the context of inflammation. To do so, we will use genetic mouse models as well as human induced pluripotent stem cells (iPSC)-derived neural cells. These are our research questions::

    1. How do IL-17 and TNF signaling in oligodendrocytes and their precursors dictate the process of de- and remyelination?
    2. How do HDAC1/2 influence demyelination in the context of EAE?
    3. How do HDAC1/2 interact with IL-17 signaling?
    4. Can pharmacological activators of HDAC2 be used as a treatment for multiple sclerosis? To elucidate this question, we will use human cells cultured in a microfluidic model of myelination.

 

 

 

 

 

 

 

 

Principal Investigators:

Univ.-Prof. Dr. rer. nat. Ari Waisman
Institut für Molekulare Medizin
Mainz
waisman@uni-mainz.de

Prof. Dr. rer. nat. Claire Jacob
Institut für Entwicklungsbiologie und Neurobiologie
Mainz
cjacob@uni-mainz.de

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