Abstract
Recent advances in neurodegenerative diseases point to novel mechanisms of protein aggregation that revolve around the unique biology of RNA binding proteins. RNA binding proteins normally are present in the nucleus. Under conditions of cell stress these RNA binding proteins translocate to the cytoplasm where they form stress granules, which function in part to sequester specialized transcript and promote translation of protective proteins. Studies in humans show that pathological aggregates occurring in ALS, Alzheimer’s disease, and other dementias co-localize with stress granules. One increasingly appealing hypothesis is that mutations in RNA binding proteins or prolonged periods of stress cause formation of very stable, pathological stress granules. The consolidation of RNA binding proteins away from the nucleus and neuronal arbors into pathological stress granules might impair the normal physiological activities of these RNA binding proteins causing the neurodegeneration associated with these diseases. Conversely, therapeutic strategies focusing on reducing formation of pathological stress granules might be neuroprotective.
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Acknowledgments
The research described above was supported by grants from NIEHS, Brightfocus foundation, Alzheimer Association, CurePSP foundation, and the Cure Alzheimer Foundation.
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Wolozin, B., Apicco, D. (2015). RNA Binding Proteins and the Genesis of Neurodegenerative Diseases. In: Vlamos, P., Alexiou, A. (eds) GeNeDis 2014. Advances in Experimental Medicine and Biology, vol 822. Springer, Cham. https://doi.org/10.1007/978-3-319-08927-0_3
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DOI: https://doi.org/10.1007/978-3-319-08927-0_3
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