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What can pluripotent stem cells teach us about neurodegenerative diseases?

Abstract

Neurodegenerative diseases represent a growing public health challenge. Current medications treat symptoms, but none halt or retard neurodegeneration. The recent advent of pluripotent cell biology has opened new avenues for neurodegenerative disease research. The greatest potential for induced pluripotent cells derived from affected individuals is likely to be their utility for modeling and understanding the mechanisms underlying neurodegenerative processes, and for searching for new treatments, including cell replacement therapies. However, much work remains to be done before pluripotent cells can be used for preclinical and clinical applications. Here we discuss the challenges of generating specific neural cell subtypes from pluripotent stem cells, the use of pluripotent stem cells to model both cell-autonomous and non-cell-autonomous mechanisms of neurodegeneration, whether adult-onset neurodegeneration can be emulated in short-term cultures and the hurdles of cell replacement therapy. Progress in these four areas will substantially accelerate effective application of pluripotent stem cells.

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Figure 1: Pluripotent cells are obtained either directly from ES cells or indirectly from somatic cells such as skin fibroblasts transformed into iPS cells by exposure to transcription factors.

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Acknowledgements

The authors are supported by US National Institutes of Health grants AG021617, NS042269, NS062180, NS064191, NS38370, NS058502 and NS055923; US Department of Defense grants W81XWH-08-1-0522, W81XWH-08-1-0465 and DAMD 17-03-1; the Parkinson Disease Foundation (New York); the Thomas Hartman Foundation For Parkinson's Research; the Project A.L.S. foundation; and the Muscular Dystrophy Association/Wings-over-Wall Street.

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Correspondence to Serge Przedborski.

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Wichterle, H., Przedborski, S. What can pluripotent stem cells teach us about neurodegenerative diseases?. Nat Neurosci 13, 800–804 (2010). https://doi.org/10.1038/nn.2577

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