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 - Category: Molecular Biology Authors: Tags: Molecular Biology of Disease, Neuroscience Articles Source Type: research

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Publication date: 18 February 2020Source: Cell Reports, Volume 30, Issue 7Author(s): Mu-Yan Cai, Connor E. Dunn, Wenxu Chen, Bose S. Kochupurakkal, Huy Nguyen, Lisa A. Moreau, Geoffrey I. Shapiro, Kalindi Parmar, David Kozono, Alan D. D’AndreaSummaryCells deficient in ataxia telangiectasia mutated (ATM) are hypersensitive to ionizing radiation and other anti-cancer agents that induce double-strand DNA breaks. ATM inhibitors may therefore sensitize cancer cells to these agents. Some cancers may also have underlying genetic defects predisposing them to an ATM inhibitor monotherapy response. We have conducted a genome-w...
Source: Cell Reports - Category: Cytology Source Type: research
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Source: Cell Reports - Category: Cytology Source Type: research
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Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
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Source: Parkinsonism and Related Disorders - Category: Neurology Authors: Source Type: research
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Source: Parkinsonism and Related Disorders - Category: Neurology Authors: Source Type: research
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Source: Journal of Medical Case Reports - Category: General Medicine Source Type: research
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Source: Animal Health Research Reviews - Category: Veterinary Research Authors: Tags: Anim Health Res Rev Source Type: research
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Source: The American Journal of Tropical Medicine and Hygiene - Category: Tropical Medicine Authors: Tags: Am J Trop Med Hyg Source Type: research
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