The Role of Glycyl-tRNA Synthetase in Neurodegeneration

随着人口平均年龄的上升，神经系统的退行性疾病带来了显著且日益增加的医疗负担。为了开发有效的治疗方法，了解这些疾病是如何产生的至关重要。相对罕见的遗传性疾病，如脊髓性肌萎缩症是一个理想的范例，所获得的见解有望广泛适用于阿尔茨海默病和帕金森病等常见疾病。我们正在研究一种由glyyl - trna合成酶（GlyRS）基因突变引起的神经退行性疾病：GlyRS是细胞所需的一种酶，用于确保蛋白质从其遗传模板中正确合成。然而，运动神经特别容易受到这种酶突变的影响。为了了解原因，我们将检查小鼠细胞，研究GlyRS突变如何改变基因表达并影响运动神经功能。然后，我们将研究这种无处不在的酶与运动神经特异性蛋白质的相互作用。通过原子结构的测定，可以确定酶介导这种相互作用的关键部分。这项研究将对神经元如何退化以及它们为什么脆弱产生新的见解。这将成为治疗这些可怕疾病的新疗法的基础。

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.