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Translating translation in Down syndrome

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Science  15 Nov 2019:
Vol. 366, Issue 6467, pp. 797-798
DOI: 10.1126/science.aaz7128

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Summary

Across the spectrum of neurological disorders, from the developmental to the degenerative, clinical features and progression are influenced not only by disease-specific genetic effects but also by more generic mechanisms. Dysregulated stress responses are emerging as common targets for therapeutic intervention independently of causal genes, offering the tantalizing prospect of new treatments for a swathe of diseases irrespective of specific etiology. The integrated stress response (ISR) is a key player in the control of proteostasis—the balance between protein synthesis and degradation that is essential for cellular health. Dysregulated proteostasis is a common feature of the neuropathological landscape, from fragile X syndrome (1) to the neurodegenerative disorders Alzheimer's and Parkinson's diseases (2). On page 843 of this issue, Zhu et al. (3) provide compelling evidence that Down syndrome (DS), the most common genetic cause of intellectual disability, joins the pantheon of neurological disorders in which dysregulated ISR signaling plays a key role.

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