The Role of Glycyl-tRNA Synthetase in Neurodegeneration

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Degenerative disorders of the nervous system place a significant and increasing healthcare burden as the average age of the population rises. In order to develop effective treatments, an understanding of how these disorders arise is critical. Relatively rare inherited diseases such as spinal muscular atrophy are an ideal paradigm with the insights gained expected to be broadly applicable to common conditions such as Alzheimer‘s and Parkinson‘s Disease. We are studying a neurodegenerative disorder caused by mutations in the gene for Glycyl-tRNA Synthetase (GlyRS): an enzyme required by cells to ensure proteins are synthesised correctly from their genetic templates. However, motor nerves are particularly vulnerable to mutations in this enzyme. To understand why, we will examine the cells of mice to study how GlyRS mutations might change gene expression and affect motor nerve function. We will then examine the interactions of this ubiquitous enzyme with proteins that may be specific to motor nerves. Through determination of the atomic structures, the key parts of the enzyme mediating such interactions can be identified. This research will yield fresh insights into how neurons degenerate and why they are vulnerable. This will then form the basis of new treatments for these appalling disorders.