ReviewInjury to the nervous system: A look into the ER

•Injury to the central or peripheral nervous system still lacks an effective treatment.•ER stress is emerging as a possible driver for neuronal dysfunction in nervous injury.•Activation of the UPR can improve cognitive and motor recovery after injury.•Therapeutic strategies to alleviate ER stress by modulating UPR are discussed.

Injury to the central or peripheral nervous systems leads to the loss of cognitive and/or sensorimotor capabilities that still lack an effective treatment. Although injury to the nervous system involves multiple and complex molecular factors, alteration to protein homeostasis is emerging as a relevant pathological mechanism. In particular, chronic endoplasmic reticulum (ER) stress is proposed as a possible driver of neuronal dysfunction in conditions such as spinal cord injury, stroke and damage to peripheral nerves. Importantly, manipulation of the unfolded protein response (UPR), a homeostatic pathway engaged by ER stress, has proved effective in improving cognitive and motor recovery after nervous system injury. Here we provide an overview on recent findings depicting a functional role of the UPR to the functional recovery after injury in the peripheral and central nervous systems.This article is part of a Special Issue entitled SI:ER stress.