Activation of the ATF6 branch of the unfolded protein response in neurons improves stroke outcome.
dc.contributor.author | Yu, Zhui | |
dc.contributor.author | Sheng, Huaxin | |
dc.contributor.author | Liu, Shuai | |
dc.contributor.author | Zhao, Shengli | |
dc.contributor.author | Glembotski, Christopher C | |
dc.contributor.author | Warner, David S | |
dc.contributor.author | Paschen, Wulf | |
dc.contributor.author | Yang, Wei | |
dc.date.accessioned | 2021-06-01T13:56:15Z | |
dc.date.available | 2021-06-01T13:56:15Z | |
dc.date.issued | 2017-03 | |
dc.date.updated | 2021-06-01T13:56:15Z | |
dc.description.abstract | Impaired function of the endoplasmic reticulum (ER stress) is a hallmark of many human diseases including stroke. To restore ER function in stressed cells, the unfolded protein response (UPR) is induced, which activates 3 ER stress sensor proteins including activating transcription factor 6 (ATF6). ATF6 is then cleaved by proteases to form the short-form ATF6 (sATF6), a transcription factor. To determine the extent to which activation of the ATF6 UPR branch defines the fate and function of neurons after stroke, we generated a conditional and tamoxifen-inducible sATF6 knock-in mouse. To express sATF6 in forebrain neurons, we crossed our sATF6 knock-in mouse line with Emx1-Cre mice to generate ATF6-KI mice. After the ATF6 branch was activated in ATF6-KI mice with tamoxifen, mice were subjected to transient middle cerebral artery occlusion. Forced activation of the ATF6 UPR branch reduced infarct volume and improved functional outcome at 24 h after stroke. Increased autophagic activity at early reperfusion time after stroke may contribute to the ATF6-mediated neuroprotection. We concluded that the ATF6 UPR branch is crucial to ischemic stroke outcome. Therefore, boosting UPR pro-survival pathways may be a promising therapeutic strategy for stroke. | |
dc.identifier | 0271678X16650218 | |
dc.identifier.issn | 0271-678X | |
dc.identifier.issn | 1559-7016 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | SAGE Publications | |
dc.relation.ispartof | Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism | |
dc.relation.isversionof | 10.1177/0271678x16650218 | |
dc.subject | Neurons | |
dc.subject | Animals | |
dc.subject | Mice | |
dc.subject | Brain Infarction | |
dc.subject | Infarction, Middle Cerebral Artery | |
dc.subject | Recovery of Function | |
dc.subject | Autophagy | |
dc.subject | Activating Transcription Factor 6 | |
dc.subject | Stroke | |
dc.subject | Gene Knock-In Techniques | |
dc.subject | Unfolded Protein Response | |
dc.subject | Neuroprotection | |
dc.title | Activation of the ATF6 branch of the unfolded protein response in neurons improves stroke outcome. | |
dc.type | Journal article | |
duke.contributor.orcid | Sheng, Huaxin|0000-0002-4325-2940 | |
duke.contributor.orcid | Yang, Wei|0000-0001-5719-4393 | |
pubs.begin-page | 1069 | |
pubs.end-page | 1079 | |
pubs.issue | 3 | |
pubs.organisational-group | Faculty | |
pubs.organisational-group | Duke | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Anesthesiology | |
pubs.organisational-group | Clinical Science Departments | |
pubs.organisational-group | Neurobiology | |
pubs.organisational-group | Duke Institute for Brain Sciences | |
pubs.organisational-group | Surgery | |
pubs.organisational-group | Anesthesiology, Neuroanesthesia | |
pubs.organisational-group | Basic Science Departments | |
pubs.organisational-group | University Institutes and Centers | |
pubs.organisational-group | Institutes and Provost's Academic Units | |
pubs.publication-status | Published | |
pubs.volume | 37 |