Amyloid-β peptide alteration of tau exon-10 splicing via the GSK3β-SC35 pathway

Kun Lin Chen, Rey Yue Yuan, Chaur Jong Hu, Chung-Yi Hsu

研究成果: 雜誌貢獻文章同行評審

14 引文 斯高帕斯(Scopus)

摘要

Amyloid-beta peptide (Aβ) and Tau protein are the lead constituents in the pathogenesis of Alzheimer's disease (AD). However, their inter-relationship in the disease process remains to be established. Tauopathy refers to a characteristic neurodegenerative process in AD. In tauopathy, Tau accumulates as a consequence of altered pre-mRNA splicing of tau exon 10, resulting in 3R (without exon 10)/4R (with exon 10) imbalance. We studied Aβ effects on tau exon 10 pre-mRNA splicing and relevant signaling events. This is the first demonstration of Aβ alteration of tau exon 10 splicing with an increase in 3R/4R ratio caused by reduced 4R expression. This Aβ βaction is causally related to its activation of GSK-3β which in turn phosphorylates SC35, an enhancer in tau exon 10 splicing. The establishment of the Aβ-GSK-3β-SC35 cascade broadens insight into development of novel strategies to modulate Aβ action on tau exon 10 splicing for possible prevention of tauopathy.
原文英語
頁(從 - 到)378-385
頁數8
期刊Neurobiology of Disease
40
發行號2
DOIs
出版狀態已發佈 - 十一月 2010

ASJC Scopus subject areas

  • Neurology

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