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Neuroscientists discover key protein responsible for controlling nerve cell protection

Findings could lead to new therapies for stroke and epilepsy

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23 April 2012

A key protein, which may be activated to protect nerve cells from damage during heart failure or epileptic seizure, has been found to regulate the transfer of information between nerve cells in the brain. The discovery, made by neuroscientists at the University of Bristol and published in Nature Neuroscience and PNAS, could lead to new therapies for stroke and epilepsy.

Golgi stained pyramidal neuron in the hippocampus of an epileptic patient. 40 times magnification. Copyright MethoxyRoxy.

Golgi stained pyramidal neuron in the hippocampus of an epileptic patient. 40 times magnification. Copyright MethoxyRoxy.

The research team, led by Professor Jeremy Henley and Dr Jack Mellor from Bristol's Medical School, has identified that a protein known as SUMO is responsible for controlling the chemical processes which reduce or enhance protection mechanisms for nerve cells in the brain.

These key SUMO proteins produce subtle responses to the brain's activity levels to regulate the amount of information transmitted by a molecule called a kainite receptor. Kainate receptor's are responsible for communication between nerve cells and can lead to epileptic seizures and nerve cell death when activated.

Dr Mellor, Senior Lecturer from the University's School of Physiology and Pharmacology, said: "Kainate receptors are a somewhat mysterious but clearly very important group of proteins that are known to be involved in a number of diseases including epilepsy. However, we currently know little about what makes kainate receptors so important. Likewise, we also know that SUMO proteins play an important role in neuroprotection. These findings provide a link between SUMO and kainate receptors that increases our understanding of the processes that nerve cells use to protect themselves from excessive and abnormal activity."

Professor Henley added: "This work is important because it gives a new perspective and a deeper understanding of how the flow of information between cells in the brain is regulated. The team has found that by increasing the amount of SUMO attached to kainate receptors - which would reduce communication between the cells - could be a way to treat epilepsy by preventing over-excitation of the brain's nerve cells."

The research teams comprised academics from the University of Bristol's MRC Centre for Synaptic Plasticity and the Division of Neuroscience in the School of Physiology & Pharmacology and the School of Biochemistry. This work was supported by the Wellcome Trust, Biotechnology and Biological Sciences Research Council (BBSRC), European Research Council (ERC), Medical Research Council (MRC) and EMBO.

ENDS

Notes to editors

Papers:

Chamberlain, SEL, González-González, IM, Wilkinson, KA, Konopacki, FA, Kantamneni, S, Henley, JM & Mellor, JR (2012). SUMOylation and phosphorylation of GluK2 regulate kainate receptor trafficking and synaptic plasticity. Nature Neuroscience (in press).

Konopacki, FA, Jaafari, N, Rocca, DL, Wilkinson, KA, Chamberlain, S, Rubin, P, Kantamneni, S, Mellor, JR & Henley, JM (2011). Agonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis. PNAS 108, 19772-7. www.pnas.org/content/108/49/19772.long

Martin, S, Nishimune, A, Mellor, JR & Henley, JM (2007). SUMOylation regulates kainate-receptor-mediated synaptic transmission. Nature 447, 321-325. www.nature.com/nature/journal/v447/n7142/full/nature05736.html

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External contact

Caroline Clancy, Press Officer, University of Bristol

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