Specific Alterations in Astrocyte Properties via the GluA2-GAPDH Complex Associated with Multiple Sclerosis

Scientific Reports
Frankie Hang Fung LeeFang Liu

Abstract

There is strong evidence indicating neuroinflammation is an important mediator in multiple sclerosis (MS), with astrogliosis playing a significant role in this process. Surprisingly, astrocytes exert paradoxical roles during disease development, but the mechanisms remain unknown. Previously, we have reported that administering an interfering peptide (GluA2-G-Gpep) which specifically disrupts the GluA2-GAPDH interaction rescued neurological symptoms in the EAE mouse model of MS. In this study, we validated that the GluA2-GAPDH complex was elevated in LPS-induced primary reactive astrocytes, and GluA2-G-Gpep treatment significantly reduced GFAP expression levels in both EAE mice and reactive astrocytes. Further in vivo and in vitro analyses revealed that GluA2-G-Gpep administration normalized EAAT1 and EAAT2 expression, rescued compromised blood-brain barrier integrity via AQP4, promoted actin reorganization and changed mitochondrial dynamics. These alterations may partially be explained by changes in the nuclear GAPDH and p53 transcription pathways. Our findings provide critical implications for understanding the astrocyte properties regulated by GluA2-GAPDH associated with MS, and insights for novel treatment options targeting ...Continue Reading

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Citations

May 22, 2019·International Journal of Molecular Sciences·Maria Ceprian, Daniel Fulton
Aug 26, 2021·Neuropharmacology·Ulyana LaloYuriy Pankratov
Nov 30, 2021·Journal of Developmental Biology·Elizabeth C CoffeyClarissa A Henry

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Methods Mentioned

BETA
co-immunoprecipitation
electrophoresis
Assay
ELISA

Software Mentioned

R
GraphPad Prism
ImageJ

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