Abstract
The prion hypothesis has extended to the fatal motor neuron disease, amyotrophic lateral sclerosis (ALS), as a means to explain the spatiotemporal spread of pathology from one or more focal points through the neuroaxis. About 20% of inheritable cases of ALS are due to mutation in the gene encoding the Cu/Zn superoxide dismutase (SOD1), causing the protein to misfold and form neurotoxic aggregates. Mutant SOD1 has been shown to impart its misfold onto natively folded wild-type SOD1 in living cells. Furthermore, misfolded wild-type SOD1 can itself induce further rounds of propagated SOD1 misfolding. Finally, this prion-like mechanism of propagated SOD1 misfolding can be transmitted from cell to cell in human cell culture. Here, we describe a protocol for the induction of wild-type SOD1 misfolding inside living cells and its subsequent transmission from cell to cell in a prion-like fashion.
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Acknowledgments
This work was supported by donations from the Allen T. Lambert Neural Research Fund and the Temerty Family Foundation, as well as by grants from PrioNet Canada and the Canadian Institutes of Health Research (CIHR).
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Grad, L.I., Pokrishevsky, E., Cashman, N.R. (2017). Intercellular Prion-Like Conversion and Transmission of Cu/Zn Superoxide Dismutase (SOD1) in Cell Culture. In: Lawson, V. (eds) Prions. Methods in Molecular Biology, vol 1658. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7244-9_24
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DOI: https://doi.org/10.1007/978-1-4939-7244-9_24
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Publisher Name: Humana Press, New York, NY
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Online ISBN: 978-1-4939-7244-9
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