Role of Neuregulin-1 in repair after SCI
Funded in: 2013, 2014, 2015
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Problem: Spinal cord injury activates endogenous repair mechanisms, but those are not entirely successful
Target: Neuregulin-1 expression and its different “variants”
Goal: Manipulate the Neuregulin-1 pathway in order to improve the repair mechanisms and enhance the functional recovery.
After a spinal cord injury (SCI) endogenous repair mechanisms are activated which partially restore function. These include remyelination of demyelinated axons, resolution of neuro-inflammation, local axonal sprouting and synaptic plasticity. Understanding and hence manipulating such endogenous repair mechanisms may provide means to enhance recovery following SCI.
Neuregulin-1 (NRG1) exists as multiple isoforms which have diverse roles in the development and plasticity of the nervous system. Expression of NRG1 on the axon has a key role in determining myelination of axons in the peripheral nervous system and within the central nervous system. NRG1 has been shown to be neuroprotective, can alter synaptic function and can also regulate the inflammatory response. Preliminary data of the research team show that NRG1 contributes to functional recovery following SCI and that remyelination of axons is dependent upon NRG1. One aim of this project is to establish how spinal cord contusion alters the expression of the different NRG-1 isoforms. A second aim is to investigate how such isoforms contribute to endogenous repair mechanisms by examining their role in remyelination, neuroprotection and the inflammatory response. Finally it will be tested if activation of this signaling pathway can improve functional recovery following SCI.
The overall goal of the project is the characterization of the NRG1 signaling system in order to learn how to manipulate this pathway to enhance recovery in spinal cord injury.