Many of the major neurodegenerative disorders are characterized by the accumulation of intracellular protein aggregates in neurons and other cells in brain, suggesting that errors in protein quality control mechanisms associated with the aging process play a critical role in the onset and progression of disease. The increased understanding of the unfolded protein response (UPR) signaling network and, more specifically, the structure and function of eIF2α phosphatases has enabled the development or discovery of small molecule inhibitors that show great promise in restoring protein homeostasis and ameliorating neuronal damage and death. While this review focuses attention on one or more eIF2α phosphatases, the wide range of UPR proteins that are currently being explored as potential drug targets bodes well for the successful future development of therapies to preserve neuronal function and treat neurodegenerative disease.
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February 2017
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Cover Image
Cover Image
The surface of the catalytic subunit of protein phosphatase PP1 (central 3D-structure) has many binding sites for regulatory proteins that are embedded in regulatory networks (coloured circles linked by lines). Please see pp. 89–99 for more information. Image provided by Mathieu Bollen.
Review Article|
February 15 2017
Translating protein phosphatase research into treatments for neurodegenerative diseases
Jeyapriya R. Sundaram;
Jeyapriya R. Sundaram
1Signature Programs in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore
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Irene C.J. Lee;
Irene C.J. Lee
1Signature Programs in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore
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Shirish Shenolikar
1Signature Programs in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore
2Signature Programs in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore
Correspondence: Shirish Shenolikar (shirish.shenolikar@duke-nus.edu.sg)
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Publisher: Portland Press Ltd
Received:
October 10 2016
Revision Received:
November 21 2016
Accepted:
November 23 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2017
Biochem Soc Trans (2017) 45 (1): 101–112.
Article history
Received:
October 10 2016
Revision Received:
November 21 2016
Accepted:
November 23 2016
Citation
Jeyapriya R. Sundaram, Irene C.J. Lee, Shirish Shenolikar; Translating protein phosphatase research into treatments for neurodegenerative diseases. Biochem Soc Trans 8 February 2017; 45 (1): 101–112. doi: https://doi.org/10.1042/BST20160157
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