See Mercado and Hetz (doi:) for a scientific commentary on this article.Signalling through the PERK/eIF2α-P branch of the Unfolded Protein Response is increased in many neurodegenerative diseases. Halliday et al. identify two safe compounds – one licensed – that act on this pathway and are neuroprotective in mice with neurodegeneration. These drugs can now be repurposed in clinical trials for the treatment of dementia.

Stroke is the second most common cause of death and the leading cause of disability in the world. About 30% of the people that are affected by stroke die within a year; 25% of the patients that survive stroke remain in need of care after a year. Therefore, stroke is a major burden for health care costs. The most common subtype is ischemic stroke. This type is characterized by a reduced and insufficient blood supply to a certain part of the brain. Despite the high prevalence of stroke, the currently used therapeutic interventions are limited. No therapies that aim to restore damaged neuronal tissue or to promote recovery are available nowadays. Transplantation of stem cell-derived cells has been investigated as a potential regenerative and protective treatment. Embryonic stem cell (ESC)-based cell therapy in rodent models of stroke has been shown to improve functional outcome. However, the clinical use of ESCs still raises ethical questions and implantation of ESC-derived cells requires continuous immunosuppression. The groundbreaking detection of induced pluripotent stem cells (iPSCs) has provided a most promising alternative. This mini-review summarizes current literature in which the potential use of iPSC-derived cells has been tested in rodent models of stroke. iPSC-based cell therapy has been demonstrated to improve motor function, decrease stroke volume, promote neurogenesis and angiogenesis and to exert immunomodulatory, anti-inflammatory effects in the brain of stroke-affected rodents.