| Autor: |
Kun-Lin Chen, Rey-Yue Yuan, Chaur-Jong Hu, Chung Y. Hsu |
| Jazyk: |
angličtina |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
Neurobiology of Disease, Vol 40, Iss 2, Pp 378-385 (2010) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2010.06.013 |
| Popis: |
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 action 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full Text from ScienceDirect