SCA8 RAN polySer protein preferentially accumulates in white matter regions and is regulated by eIF3F

We report a novel toxic SCA8 polySer protein which accumulates in white matter (WM) regions as aggregates that increase with age and disease severity. WM regions with polySer aggregates show demyelination and axonal degeneration in SCA8 human and mouse brains. Additionally, knockdown of the eukaryotic translation initiation factor eIF3F in cells reduces steady-state levels of SCA8 polySer and other RAN proteins. Taken together, these data show polySer and WM abnormalities contribute to SCA8 and identify eIF3F as a novel modulator of RAN protein accumulation.

Source: EMBO Journal - October 1, 2018 Category: Molecular Biology Authors: Ayhan, F., Perez, B. A., Shorrock, H. K., Zu, T., Banez-Coronel, M., Reid, T., Furuya, H., Clark, H. B., Troncoso, J. C., Ross, C. A., Subramony, S., Ashizawa, T., Wang, E. T., Yachnis, A. T., Ranum, L. P. Tags: Molecular Biology of Disease, Neuroscience Articles Source Type: research