Transcriptome analyses of chronic traumatic encephalopathy show alterations in protein phosphatase expression associated with tauopathy

Experimental & Molecular Medicine
Jeong-Sun SeoAnn C McKee

Abstract

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer's disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel ther...Continue Reading

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Citations

Jun 22, 2018·Neural Regeneration Research·Liam Chen
Jul 19, 2019·Frontiers in Neuroscience·Gestter W L TessarinCláudio A Casatti
Aug 5, 2020·Nature Biotechnology·Volker BergenFabian J Theis
Nov 26, 2019·Neurobiology of Disease·Hank ChengAndrew M Schumacher
Jun 25, 2018·Neurobiology of Disease·Patricia G SalettiAristea S Galanopoulou
Mar 24, 2021·Cell Death and Differentiation·Jong-Heon KimKyoungho Suk
May 22, 2021·Acta Neuropathologica·K Blake ChancellorAnn C McKee
Jun 27, 2021·Molecular Neurodegeneration·Laura Gutierrez-QuicenoChadwick M Hales

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Methods Mentioned

BETA
PCR
transgenic
RNA-Seq
fluorescence imaging

Software Mentioned

Ensembl
LightCyler96
R
Harmony
STAR
GSEA
R package
Java
WGCNA
Treeview

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