Skip to main content

Glutamate receptor proteins as novel neuroprotective targets

Final Report Summary - GRIPANNT (Glutamate Receptor Proteins as Novel Neuroprotective Targets)

Glutamate receptor interacting proteins (interactors) serve dual purpose. They determine the level and site of glutamate receptor expression within the cells and connect the receptors to specific intracellular signalling pathways. Both roles are interesting from a therapeutical perspective. The present project has identified novel interactors and has provided new insight in the principles that govern the turnover and surface expression of glutamate receptors. The GRIPANNT project's work has also led to the elucidation of genes and intracellular signalling pathways that regulate cell death and cell survival. In sum, the data that have been generated in the project period have established a platform for new approaches to alleviate excitotoxic cell loss in the central nervous system.

The project has led to the publication of 130 papers in international peer reviewed journals. Many of the papers have appeared in top tier journals. Thus the list includes 1 paper in Nature, 1 in Science, 8 in Neuron, 11 in the Journal of Neuroscience, 3 in PNAS, 1 in Nature Neuroscience, 2 in EMBO Journal, and 1 in the Journal of Cell Biology. Dissemination of results has also been secured through a number of high profile reviews, including two reviews in Nature Neuroscience Reviews and several reviews and commentaries in Neuron and other leading journals. In addition, the work has been summarised and discussed in a separate special issue, published in Neuroscience - the official journal of the International Brain Research Organisation. This special issue (published in January 2009) is entitled 'Protein trafficking, targeting and interaction at the glutamate synapse' and contains more than 40 contributions. The coordinator of GRIPANNT (O. P. Ottersen) acted as chief editor of this special issue and two GRIPANNT partners were among the guest editors.

Several of the novel cytoprotective strategies identified in previous work packages were evaluated in vivo. Specifically, antagonists of glutamate receptor binding proteins were tested in in vivo models of stroke, as were peptides that interfere with glutamate receptor anchoring (such as the GluR6b C-terminal peptides that were developed in earlier work packages). The project's results do not support a protective effect in excitotoxic disorders but the compounds may represent a treatment strategy for other diseases such as pain.

Related documents