Halting neuron damage with glutamate receptor proteins
The cause of neuron cell death in a number of neurodegenerative diseases is due to excitotoxicity. Nerve damage and death in stroke, head trauma and the genetic disorder Huntington's disease can all be induced by an excess of neurotransmitters, one of the main ones being glutamate. Research into glutamate has revealed proteins that anchor and interact with glutamate receptors thus potentially avoiding neuronal damage and apoptosis. With this new strategic approach to cytoprotective therapy, the 'Glutamate receptor proteins as novel neuroprotective targets' (Grippannt) project aimed to use glutamate receptor proteins (interactors) as a basis for novel therapies. Interactors determine the level and place of glutamate receptor expression as well as connect the receptors to specific cell pathways, therefore offering two potential avenues for therapeutic development. Grippant scientists aimed to reduce excitotoxicity by modulating the surface expression of glutamate receptors thereby interfering with their signalling activities. Grippant research led to the identification of genes involved as well as biochemical pathways that induce the choice between cell death and survival. Specifically, antagonistic molecules that would prevent glutamate receptor binding were tested using in vivo models of stroke as well as peptides that interfere with glutamate receptor anchoring. Dissemination of Grippant results included the publication of more than 130 papers in top science journals. An account of the work in its entirety was summarised and discussed in a special issue of Neuroscience the official journal of the International Brain Research Organisation. Published in January 2009, 'Protein trafficking, targeting and interaction at the glutamate synapse' contains more than 40 contributions. Although the results do not as yet offer a neuroprotection against excitotoxicity, they may be applicable to other therapies, for example pain relief. Data generated overall provides a basis for further research into the alleviation of excitotoxic cell loss in the central nervous system.
