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NEURODEVELOPMENTAL DISORDERS

Integrated stress response mediates cognitive decline in Down syndrome

Nature Reviews Neurology volume 16, page 3 (2020)Cite this article

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Down syndrome (DS), a neurodevelopmental disorder that results from the presence of an extra copy of chromosome 21, is a common cause of intellectual disability in the general population, but little is known about the molecular mechanisms that underlie the cognitive deficits. In a new study published in Science, Mauro Costa-Mattioli, Peter Walter and colleagues provide evidence that a signalling network known as the integrated stress response (ISR) mediates cognitive decline in DS.

The ISR is an evolutionarily conserved pathway, the normal role of which is to regulate protein synthesis under conditions of cellular stress. To investigate the relationship between the ISR and cognitive impairment in DS, Costa-Mattioli and colleagues used the Ts65Dn mouse model, which recapitulates the types of cognitive deficit that are observed in humans with this condition.

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References

Original article

  • Zhu, P. J. et al. Activation of the ISR mediates the behavioral and neurophysiological abnormalities in Down syndrome. Science 366, 843–849 (2019)

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  • Lott, I. T. & Head, E. Dementia in Down syndrome: unique insights for Alzheimer disease research. Nat. Rev. Neurol. 15, 135–147 (2019)

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  1. Nature Reviews Neurology http://www.nature.com/nrneurol/

    Heather Wood

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  1. Heather Wood
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Correspondence to Heather Wood.

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Wood, H. Integrated stress response mediates cognitive decline in Down syndrome. Nat Rev Neurol 16, 3 (2020). https://doi.org/10.1038/s41582-019-0298-6

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