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

Title
Transcriptome analyses of chronic traumatic encephalopathy show alterations in protein phosphatase expression associated with tauopathy
Authors
김동진김종현김윤경황은미류훈현승재Jeong-Sun SeoSeungbok LeeJong-Yeon ShinYu Jin HwangHyesun ChoSeong-Keun YooYunha KimSungsu LimSu Hyun KimJi-Young YunJihye KimYona KimVictor E AlvarezThor D SteinJunghee LeeJong-Il KimNeil W KowallAnn C McKee
Issue Date
2017-05
Publisher
Experimental & molecular medicine
Citation
VOL 49-e333-12
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 therapeutic approaches to reduce the tauopathy associated with CTE.
URI
https://pubs.kist.re.kr/handle/201004/65733
ISSN
1226-3613
Appears in Collections:
KIST Publication > Article
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