UNDERSTANDING THE ROLE OF GARS IN CHARCOT-MARIE-TOOTH DISEASE
Charcot-Marie-Tooth disease (CMT) is a type of inherited peripheral neuropathy which causes degeneration of motor and sensory axons, leading to symptoms such as progressive muscle weakness and sensory loss, numbness, and pain. CMT neuropathies are among the most common types of hereditary neurological conditions, affecting 1 in 2,500 people who currently have no treatment options aside from managing the symptoms. Over 70 genes that play a role in a variety of cellular processes have been found to be associated with CMT. This highlights the diversity and complexity of the disease, but also begins to provide insight on potential therapeutic approaches to treating it. CMT2D is a specific type of CMT caused by dominant mutations in the GARS gene, which codes for glycyl-tRNA synthetase. The reasoning behind the specificity of the phenotypes seen in CMT2D is unclear, as the translational function of GARS is necessary in nearly all cell types. The association of GARS and CMT2D indicates that it also has a role in maintaining peripheral neurons, but the mechanisms remain unknown. We find that the stress response protein, p38 MAPK (p38Kb) regulates the protein levels of GARS with aging. Loss of p38Kb causes locomotor dysfunction and loss of sensation, similar to the symptoms seen in CMT. Using the established CMT model Drosophila Melanogaster to determine the mechanisms by which GARS and p38Kb interact to promote neuromuscular health, we may shed light on how to develop molecular therapeutics to treat CMT2D.
Martin, Julia, "UNDERSTANDING THE ROLE OF GARS IN CHARCOT-MARIE-TOOTH DISEASE" (2019). University Research Symposium. 327.