Cellular and molecular mechanisms of tumor necrosis factor receptor 2 mediated neuroprotection in spinal cord injury

• Applicant: Dr. Roman Fischer
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Cell Biology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 286456974

Tumor necrosis factor (TNF) is a multifunctional cell signaling protein that plays a dual role in neurodegenerative diseases. Signaling mediated via TNF receptor 1 (TNFR1) promotes inflammation and tissue degeneration, whereas signaling via TNFR2 contributes to neuroprotection and tissue regeneration. Due to this important regenerative role of TNFR2, molecules that specifically activate TNFR2 could promote recovery in neurodegenerative diseases. To continue my previous work, where I developed the first clinically applicable TNFR2 agonist, I now want to investigate the therapeutic efficacy of this molecule in traumatic spinal cord injury. In these studies, the therapeutic outcome will be monitored by behavioral and histological analyses as well as electrophysiological assessments. In particular, by using transgenic mice, where TNFR2 can be inducible knocked-out in specific glial cells, it will be possible to identify cellular and molecular mechanism underlying the anti-inflammatory and regenerative effects mediated via TNFR2 signaling. The intended studies in the spinal cord injury model will pave the way for possible clinical trials with TNFR2 agonists in neurodegenerative diseases and may lead to the development of a therapy for traumatic spinal cord injury.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. John R. Bethea