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Understanding death-receptor signaling and physiology in the nervous system: A roadmap for the development of new treatments to neurodegenerative diseases and neurotrauma

Final Report Summary - P75NTR (Understanding death-receptor signaling and physiology in the nervous system: A roadmap for the development of new treatments to neurodegenerative diseases and neurotrauma)

This project has unraveled the mechanism by which the death receptor p75NTR contributes to fundamental aspects of neuron maintenance and function, including responses to neurodegeneration and injury. Signaling by p75ntr receptor exerts a variety of effects on neuron survival, indicating that compounds able to modulate p75NTR function may have beneficial effects in neurodegenerative diseases and cancer. In this project, we have elucidated the molecular mechanisms by which p75NTR and other death receptors become activated by different ligands and elicit distinct, ligand-specific cellular responses. We have unravelled the physiological significance of distinct p75NTR signaling pathways through genetic dissection with pathway-specific mutants in knock-in mice. Finally, We have identified and characterized novel small molecule p75NTR modulators. These may represent new therapeutics for the treatment of cancer and neurodegeneration.