Protein aggregates characterize Huntington's disease(HD), and are responsible for the neurodegeneration and loss of function that leads to the devastating symptoms faced by HD patients. Loss of neuronal functioning occurs because over time, aggregates recruit other proteins such as molecular chaperones, which are mediators of vital cellular processes, into the inclusion bodies. Sequestration of chaperones such as Hsc70 into inclusion bodies depletes the amount available to mediate crucial pathways such as such as endocytosis, autophagy, and stress response, resulting in their collapse, which ultimately results in loss of cellular homeostasis, and functioning. We propose to rescue functioning of HD cells by delivering chaperone Hsc70 through direct protein transduction. Protein transduction can be accomplished by fusing Hsc70 to a cell penetrating peptide, TAT, which has been shown facilitate interactions with the cell membrane that allow protein to enter into the cell cytosol.
|Effective start/end date||6/1/14 → 8/31/14|
- Huntington's Disease Society of America (Letter 4/17/14)
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