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The role of JNK/c-Jun pathway in axonal damage and neuronal regeneration

Objective

Interruption of axons results in a characteristic reaction of the injured neuron, the so-called axonal response, which aims to induce axon elongation and to achieve a re-construction of effective synapses. Nerve fiber transection elicits a complex neuronal response that leaves neurons poised between death and regeneration. Although the signals underlying this dichotomy are not fully understood, some are mediated by the induction of immediate-early transcription factors of the AP-1 family, a key regulator in crucial cellular events. AP-1 activity is regulated, in part, by the phosphorylation of its c-Jun component by the Jun N-terminal Kinases (JNKs). Recent work has confirmed the notion that c-Jun functions as the trigger of the axonal response during neuronal regeneration in the CNS and strongly supports the perception of c-Jun action as a “double-edged sword” promoting post-traumatic neuronal cell death as well as axonal regeneration. The goal of this project is to better understand the function of the JNK/c-Jun pathway during neuronal regeneration by generating and employing gain and loss-of-function transgenic mice models and to clarify the role of JNKs/c-Jun phosphorylation in the neuronal response to axonal damage. The assessment of the reinnervation after injury in these transgenic lines will use suitable regeneration paradigms. We are also interested in identifying new JNK/c-Jun mediators that could play a role in the axonal response to injury. Thus, future perspectives towards the strengthening of European potential research could derive from this study. This project integrates well in the FP7 program, and will applicate knowledge and biotechnology for health. The accomplishment of the project would contribute significantly to the acquisition of new relevant data on JNK functions in neuronal death and axonal regeneration, which is indispensable to predict the outcome of JNK/c-Jun system inhibition as a putative therapeutical strategy.

Call for proposal

FP7-PEOPLE-IEF-2008
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Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

CANCER RESEARCH UK LBG
Address
St John Street 407 Angel Building
EC1V 4AD London
United Kingdom
Activity type
Research Organisations
EU contribution
€ 171 867,63
Administrative Contact
Holly Elphinstone (Ms.)