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

• Published in: Experimental & molecular medicine 2017-05, Vol.49 (5), p.e333-e333
• Main Authors: Seo, Jeong-Sun, Lee, Seungbok, Shin, Jong-Yeon, Hwang, Yu Jin, Cho, Hyesun, Yoo, Seong-Keun, Kim, Yunha, Lim, Sungsu, Kim, Yun Kyung, Hwang, Eun Mi, Kim, Su Hyun, Kim, Chong-Hyun, Hyeon, Seung Jae, Yun, Ji-Young, Kim, Jihye, Kim, Yona, Alvarez, Victor E, Stein, Thor D, Lee, Junghee, Kim, Dong Jin, Kim, Jong-Il, Kowall, Neil W, Ryu, Hoon, McKee, Ann C
• Format: Article
• Language: English
• Subjects: 45/91; 631/378/368; 692/699/375; Aged; Aged, 80 and over; Alzheimer's disease; Animal models; Animals; Biomedical and Life Sciences; Biomedicine; Brain injury; Calcineurin; Calcineurin - genetics; Calcineurin - metabolism; Calcium Signaling; Calcium signalling; Cell culture; Cell lines; Chronic Traumatic Encephalopathy - genetics; Chronic Traumatic Encephalopathy - metabolism; Chronic Traumatic Encephalopathy - pathology; Down-Regulation; Encephalopathy; Female; Gene expression; HEK293 Cells; Humans; Kinases; Male; MAP kinase; MAP Kinase Signaling System; Medical Biochemistry; Mice; Mice, Inbred C57BL; Middle Aged; Molecular Medicine; Neurodegeneration; Neurodegenerative diseases; Neuropathology; Original; original-article; Phosphatase; Phosphorylation; Protein phosphatase; Protein Processing, Post-Translational; Ribonucleic acid; RNA; Stem Cells; Tau protein; tau Proteins - metabolism; Transcriptome
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/emm.2017.56

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. Chronic traumatic encephalopathy: Gene expression analysis reveals similarities to Alzheimer's Chronic traumatic encephalopathy (CTE) and Alzheimer's disease share common disease mechanisms, according to recent research on human brains. Jeong-Sun Seo and colleagues from Seoul National University, South Korea, and Hoon Ryu, Ann McKee and collegues from Boston University, USA sequenced all the RNA found in post-mortem brain tissue taken from six people with CTE, a progressive neurodegenerative disorder caused by repeated blows to the head, and compared the expression profile with seven normal control individuals. The researchers found that genes in two important signaling pathways were significantly less active in people with CTE. Altered expression of certain genes in these pathways suggested that the buildup of the aberrant tau protein in CTE occurs by a similar mechanism to that seen in Alzheimer's disease. Experiments in cell lines and mouse models substantiated this finding.