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

• Published in: Experimental & molecular medicine 2017, 49(0), , pp.1-12
• Main Authors: 서정선, 이승복, 신종연, 황유진, 조혜선, 유승근, 김윤하, 임성수, 김윤경, 황은미, 김수현, 김종현, 현승재, 윤지영, 김지혜, 김요나, Victor E Alvarez, Thor D Stein, 이정희, 김동진, 김종일, Neil W Kowall, 류훈, Ann C McKee
• Format: Article
• Language: English
• Subjects: 생화학
• ISSN: 1226-3613; 2092-6413

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 therapeutic approaches to reduce the tauopathy associated with CTE. KCI Citation Count: 8