Abstract
Misfolded proteins have been implicated in most of the major neurodegenerative diseases, and identifying drugs and pathways that protect neurons from the toxicity of misfolded proteins is of paramount importance. We invented a form of automated imaging and analysis called robotic microscopy that is well suited to the study of neurodegeneration. It enables the monitoring of large cohorts of individual neurons over their lifetimes as they undergo neurodegeneration. With automated analysis, multiple endpoints in neurons can be measured, including survival. Statistical approaches, typically reserved for engineering and clinical medicine, can be applied to these data in an unbiased fashion to discover whether factors contribute positively or negatively to neuronal fate and to quantify the importance of their contribution. Ultimately, multivariate dynamic models can be constructed from these data, which can provide a systems-level understanding of the neurodegenerative disease process and guide the rationale for the development of therapies.
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Acknowledgments
This work was supported by R01 2NS039746 and 2R01 NS045191 from the National Institute of Neurological Disease and Stroke, P01 2AG022074 from the National Institute on Aging, and the Gladstone Institutes (S.F.), the Milton Wexler Award, and a fellowship from the Hereditary Disease Foundation (A.T.). Gladstone Institutes received support from a National Center for Research Resources Grant RR18928-01. Kelley Nelson provided administrative assistance, and Gary C. Howard and Anna Lisa Lucido edited the manuscript.
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Tsvetkov, A.S., Ando, D.M., Finkbeiner, S. (2013). Longitudinal Imaging and Analysis of Neurons Expressing Polyglutamine-Expanded Proteins. In: Hatters, D., Hannan, A. (eds) Tandem Repeats in Genes, Proteins, and Disease. Methods in Molecular Biology, vol 1017. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-438-8_1
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DOI: https://doi.org/10.1007/978-1-62703-438-8_1
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