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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)378-385
Number of pages8
JournalNeurobiology of Disease
Volume40
Issue number2
DOIs
Publication statusPublished - Nov 2010

Keywords

  • Alzheimer's disease
  • Corticobasal degeneration
  • Fronto-temporal dementia
  • GSK3β
  • Progressive supranuclear palsy
  • SC35
  • SH-SY5Y
  • Tau exon 10 splicing
  • Tauopathy

ASJC Scopus subject areas

  • Neurology

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