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A reduction in the RNA binding protein TIA1 protects against neurodegeneration, rescues behavioral deficits and prolongs survivalRandhawa, Anantbir 24 July 2018 (has links)
RNA binding proteins (RBPs) have been found to be frequently involved in neurodegenerative diseases (Ash 2014). Mutations in RBPs cause amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia, frontotemporal dementia (FTD) and myopathies (Ash 2014), and recent studies suggest that aggregation of RBPs are a pathological feature frequently encountered in tauopathies (Vanderweyde 2016). Emerging studies on neurodegenerative diseases are now showing an increasingly important role for tau in regulating the biology of RBPs. In this study, we examine findings that show that reducing the RBP T-cell intracellular antigen 1 (TIA1) in vivo not only protects against neurodegeneration, but also prolongs the survival rate in transgenic P301S tau mice. Furthermore, the reduction of TIA1 decreases the number and size of granules co-localizing with stress granule markers, and inhibits the accumulation of tau oligomers, although at the expense of an increased number of neurofibrillary tangles. However, despite the observed increase in neurofibrillary tangles, this TIA1 reduction still manages to increase neuronal survival, rescue behavioral deficits and prolong lifespan. The in vivo data presented in this study suggests an important role for TIA1 in mediating toxicity and provides evidence that RBPs orchestrate a pathway to tau aggregation and the resulting neurodegeneration.
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