"Repulsive guidance cues for growing axons and factors inhibiting neurite growth are increasingly recognized as key players for nerve fiber growth and plasticity in the developing and adult nervous system. The first neurite growth inhibitory factor discovered in the context of axonal regeneration in the adult central nervous system (CNS) was the membrane protein Nogo-A. Inactivation of Nogo-A, e.g. by neutralizing antibodies, after spinal cord injury, brain injury or stroke leads to improved functional recovery in parallel with long distance regeneration of injured fibers and enhanced compensatory sprouting. The molecular mechanisms of action of Nogo-A is only partially known; a key element, the Nogo-A-specific receptor has remained undefined. We have recently found a membrane protein that binds to Nogo-A with high affinity; blockers of this new receptor neutralize many of the typical Nogo-A effects in vitro. The present proposal addresses new aspects of the mechanism of action and the in vivo roles of this novel Nogo-A receptor and its interactions with the known Nogo receptor components.
The new results will contribute to the molecular and physiological understanding of Nogo-A and related growth inhibitors in the nervous system. Together with the currently ongoing clinical trial to enhance recovery after spinal cord injury in patients by anti-Nogo-A antibodies, the results of the present project will form an important basis for further treatments in brain injury and stroke."
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