Searching across hundreds of databases
Vanishing white matter disease (VWMD) is an inherited autosomal-recessive hypomyelinating disease caused by mutations in eukaryotic translation initiation factor 2B (eIF2B). eIF2B mutations predominantly affect the brain white matter, and the characteristic features of VWMD pathology include myelin loss and foamy oligodendrocytes. Activation of pancreatic endoplasmic reticulum kinase (PERK) has been observed in oligodendrocytes in VWMD. PERK activation in response to endoplasmic reticulum stress attenuates eIF2B activity by phosphorylating eIF2α, suggesting that impaired eIF2B activity in oligodendrocytes induced by VWMD mutations or PERK activation exploit similar mechanisms to promote selective white matter pathology in VWMD. Using transgenic mice that allow for temporally controlled activation of PERK specifically in oligodendrocytes, we discovered that strong PERK activation in oligodendrocytes during development suppressed eIF2B activity and reproduced the characteristic features of VWMD in mice, including hypomyelinating phenotype, foamy oligodendrocytes, and myelin loss. Notably, impaired eIF2B activity induced by PERK activation in oligodendrocytes of fully myelinated adult mice had minimal effects on morphology or function. Our observations point to a cell-autonomous role of impaired eIF2B activity in myelinating oligodendrocytes in the pathogenesis of VWMD.
Pubmed ID: 25186761 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets Phospho-eIF2alpha (Ser51)
View all literature mentionsThis monoclonal targets APC
View all literature mentionsThis monoclonal targets Puromycin from Streptomyces alboniger
View all literature mentionsThis monoclonal targets Casp3
View all literature mentionsThis monoclonal targets Myelin Basic Protein (SMI 99) Purified
View all literature mentionsThis polyclonal targets Actin N-terminal antibody produced in rabbit
View all literature mentionsThis polyclonal targets Phospho-eIF2alpha (Ser51)
View all literature mentionsStatistical analysis and scientific graphing software for Windows OS.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsThis polyclonal targets Phospho-eIF2alpha (Ser51)
View all literature mentionsThis monoclonal targets APC
View all literature mentionsThis polyclonal targets Phospho-eIF2alpha (Ser51)
View all literature mentionsThis monoclonal targets Casp3
View all literature mentionsThis polyclonal targets Actin N-terminal antibody produced in rabbit
View all literature mentionsThis monoclonal targets Myelin Basic Protein (SMI 99) Purified
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
