Investigating the Oligomerization of TorsinA as a Means to Develop DYT1 Dystonia Therapeutics
Technical Report,15 Aug 2018,14 Aug 2019
Massachusetts Institute of Technology Cambridge United States
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Dystonia is movement disorder than manifests itself in repetitive, involuntary muscle contractions, affecting parts focal or the entire general human body. A glutamate deletion deltaE in the enzyme Torsin A triggers the most common form of generalized dystonia, Toxins and traumatic brain injury can also trigger dystonia. The molecular mechanism of the disease is unclear. In this project we are examining the three-dimensional structure of TorsinA, particularly its filamentous form, and to develop we are establishing assays to screen for effector molecules that will rescue the enzymatic activity of TorsinAdeltaE. In this progress report we lay out the advances that have been made in the first year of the funding period. We have published the filamentous structure of TorsinA, which was our first specific Aim. We are now engaged in improving the resolution of the published structure, and we are trying to establish a membrane-bound form of the protein. To develop the functional assays, we are in the process of establishing a procedure to produce milligram quantities of TorsinA at high purity.
- Anatomy and Physiology