As life expectancies across the world continue to increase, the number of people suffering from a degenerative neurological disorder such as Parkinson’s disease and Alzheimer’s disease also rapidly increases. This is a significant problem (particularly in the developed world), with sufferers regularly experiencing a poor quality of life which often leaves them requiring costly round-the-clock care. Current pharmaceuticals have had some success in treating specific neurological disorders, but their effects are significantly limited as they generally only slow the progression of the disease. Consequently, there is a significant need for new and innovative methods to treat these debilitating neurological conditions. Researchers have established that some neurological disorders are caused by the break-down of neural networks in the brain. This has since been linked to the malfunction of glutamate receptors (GluRs) found in the cell membranes of neurons. In this Fellowship, we propose that new families of photochromic ligands (PCLs) that selectively and reversibly control GluRs using light, could be used to 'reactivate' unresponsive neural networks in the brain, allowing for the development of new and pioneering treatments for neurological disorders. To accomplish this we will develop new PCLs that are 'turned-on' by low energy 'red-shifted' light and then are rapidly 'turned-off' in the dark. This will significantly advance the current state of the art PCLs which are 'turned-on' in the dark, making them unsuitable for therapeutic applications. The new PCLs will target GluRs that are selectively expressed in particular cell types in the brain that are linked with the onset of degenerative neurological diseases. This will allow us to extensively study the role these GluRs play in the onset of neurological disorders, thus enabling us to develop new methods to treat these debilitating diseases.
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