Abstract Initial Draft

Dystonia is a neuromuscular disorder in which muscles make involuntary contractions, leading to abnormal and often times repetitive movements. It has been found that a common mechanism for several types of dystonia—each characterized by the gene adversely affected—was an impairment in ISR signaling. (Rittiner, et al,) Furthermore, the alleles causing dystonia have incomplete penetrance. Thus, individuals who have the dGAG mutation for dystonia could either be manifesting—individuals who exhibit the disorder—or non-manifesting—individuals who do not have the disorder but have the mutation. This project will focus on this idea of manifesting and non-manifesting patients with the dGAG mutation through the examination of exosomes and other extracellular vesicles. Specifically, this research explores the potential for exosomes to be biomarkers for the difference in manifesting and non-manifesting disease states, because exosomes are known for their role in intracellular communication and disease progression. To test this possibility, ultracentrifugation is being utilized to isolate exosomes from patient fibroblasts grown in conditioned media. Then, a bicinchoninic acid assay was run to examine protein content in both cell lysates and extracellular vesicle samples. For further testing, the plan is to run a western blot utilizing antibodies that will indicate whether or not exosomes were enriched, and then to send these samples to another lab for further testing. Potential results would be that there may be a difference in the RNA and protein composition of the exosomes between the manifesting and non-manifesting. There may also be a difference in the production of exosomes between the manifesting and non-manifesting. Finally, there could be no significant difference between these states.

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