1.Transcriptome analyses of chronic traumatic encephalopathy show alterations in protein phosphatase expression associated with tauopathy.
Jeong Sun SEO ; Seungbok LEE ; Jong Yeon SHIN ; Yu Jin HWANG ; Hyesun CHO ; Seong Keun YOO ; Yunha KIM ; Sungsu LIM ; Yun Kyung KIM ; Eun Mi HWANG ; Su Hyun KIM ; Chong Hyun KIM ; Seung Jae HYEON ; Ji Young YUN ; Jihye KIM ; Yona KIM ; Victor E ALVAREZ ; Thor D STEIN ; Junghee LEE ; Dong Jin KIM ; Jong Il KIM ; Neil W KOWALL ; Hoon RYU ; Ann C MCKEE
Experimental & Molecular Medicine 2017;49(5):e333-
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.
Alzheimer Disease
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Brain
;
Brain Injury, Chronic*
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Cell Line
;
Craniocerebral Trauma
;
Gene Expression Profiling*
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Humans
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Models, Animal
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Neurodegenerative Diseases
;
Phosphoprotein Phosphatases
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Phosphotransferases
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Sequence Analysis, RNA
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Tauopathies*
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Transcriptome*
Result Analysis
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