Role of Tob1 - a member of the anti-proliferative (APRO) family - in experimental autoimmune encephalomyelitis and motor neuron dysfunction

• Applicant: Dr. Ulf Schulze Topphoff
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2010 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 185457936

Multiple sclerosis (MS) is a common autoimmune disease of the central nervous system. Despite massive efforts, very little is known about the mechanisms that are involved during the early stages of MS. Recently, we identified a strong correlation between the anti-proliferative gene TOB1 (Tob1 in mice) and the rapid progression of individuals with clinically isolated syndrome (CIS) to the clinically definite form of MS (CDMS). Therefore, we hypothesized that Tob1 might be intimately involved in the pathogenic mechanisms underlying the development and progression of MS and its animal model EAE. This hypothesis is supported by our preliminary data that clearly revealed the implication of Tob1 in initial immune responses during EAE. To our surprise, we further revealed an unexpected involvement of Tob1 in early motor neuron dysfunction during neuroinflammation. Thus, this proposal aims to dissect the role(s) of Tob1 in controlling both initial immune responses and motor neuron activity using the animal model of MS, EAE. The identification of factors involved in the conversion of CIS to CDMS will not only help us understanding MS pathogenesis and development but will also reveal novel targets for early therapies, which may contribute to modulate disease progression in the very early phase of the disease.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Jorge R. Oksenberg