UPR Responsive Genes Manf and Xbp1 in Stroke

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http://hdl.handle.net/10138/346279

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Lohelaid , H , Anttila , J E , Liew , H-K , Tseng , K-Y , Teppo , J , Stratoulias , V & Airavaara , M 2022 , ' UPR Responsive Genes Manf and Xbp1 in Stroke ' , Frontiers in Cellular Neuroscience , vol. 16 , 900725 . https://doi.org/10.3389/fncel.2022.900725

Title: UPR Responsive Genes Manf and Xbp1 in Stroke
Author: Lohelaid, Helike; Anttila, Jenni E.; Liew, Hock-Kean; Tseng, Kuan-Yin; Teppo, Jaakko; Stratoulias, Vassilis; Airavaara, Mikko
Contributor organization: Neuroscience Center
Division of Pharmacology and Pharmacotherapy
Division of Pharmaceutical Chemistry and Technology
Divisions of Faculty of Pharmacy
Helsinki Institute of Sustainability Science (HELSUS)
Drug Research Program
Date: 2022-06-15
Language: eng
Number of pages: 22
Belongs to series: Frontiers in Cellular Neuroscience
ISSN: 1662-5102
DOI: https://doi.org/10.3389/fncel.2022.900725
URI: http://hdl.handle.net/10138/346279
Abstract: Stroke is a devastating medical condition with no treatment to hasten recovery. Its abrupt nature results in cataclysmic changes in the affected tissues. Resident cells fail to cope with the cellular stress resulting in massive cell death, which cannot be endogenously repaired. A potential strategy to improve stroke outcomes is to boost endogenous pro-survival pathways. The unfolded protein response (UPR), an evolutionarily conserved stress response, provides a promising opportunity to ameliorate the survival of stressed cells. Recent studies from us and others have pointed toward mesencephalic astrocyte-derived neurotrophic factor (MANF) being a UPR responsive gene with an active role in maintaining proteostasis. Its pro-survival effects have been demonstrated in several disease models such as diabetes, neurodegeneration, and stroke. MANF has an ER-signal peptide and an ER-retention signal; it is secreted by ER calcium depletion and exits cells upon cell death. Although its functions remain elusive, conducted experiments suggest that the endogenous MANF in the ER lumen and exogenously administered MANF protein have different mechanisms of action. Here, we will revisit recent and older bodies of literature aiming to delineate the expression profile of MANF. We will focus on its neuroprotective roles in regulating neurogenesis and inflammation upon post-stroke administration. At the same time, we will investigate commonalities and differences with another UPR responsive gene, X-box binding protein 1 (XBP1), which has recently been associated with MANF's function. This will be the first systematic comparison of these two UPR responsive genes aiming at revealing previously uncovered associations between them. Overall, understanding the mode of action of these UPR responsive genes could provide novel approaches to promote cell survival.
Subject: ARMET
CDNF
ER stress
IRE1
mesencephalic astrocyte-derived neurotrophic factor
unfolded protein response
XBP1
ENDOPLASMIC-RETICULUM STRESS
UNFOLDED PROTEIN RESPONSE
NEUROTROPHIC FACTOR MANF
CEREBRAL-ARTERY OCCLUSION
S-METHYL-N
ER STRESS
ADULT NEUROGENESIS
O-GLCNACYLATION
MESSENGER-RNA
CELL-DAMAGE
3112 Neurosciences
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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