Molecular Cell
Volume 66, Issue 6, 15 June 2017, Pages 761-771
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Review
The UPRER: Sensor and Coordinator of Organismal Homeostasis

https://doi.org/10.1016/j.molcel.2017.05.031Get rights and content
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Life is stressful. Organisms are repeatedly exposed to stressors that disrupt protein homeostasis (proteostasis), resulting in protein misfolding and aggregation. To sense and respond to proteotoxic perturbations, cells have evolved compartment-specific stress responses, such as the unfolded protein response of the endoplasmic reticulum (UPRER). However, UPRER function is impaired with age, which, we propose, creates a permissive environment for protein aggregation, unresolved ER stress, and chronic inflammation. Understanding age-related changes to the UPRER will provide new avenues for therapeutic intervention in metabolic disease, neurodegeneration, and aging.

Keywords

endoplasmic reticulum
unfolded protein response
ER stress
protein aggregation
chronic inflammation
aging
metabolic disease
amyotrophic lateral sclerosis
XBP1
NF-kappaB

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