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SLM, a novel carbazole-based fluorophore attenuates okadaic acid-induced tau hyperphosphorylation via down-regulating GSK-3 beta activity in SH-SY5Y cells
Wu, Xiaoli; Kosaraju, Jayasankar; Tam, Kin Yip
2017-12-15
Conference NameEUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume110
Pages101-108
Publication PlacePO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
PublisherELSEVIER SCIENCE BV
AbstractPhosphorylated tau dissociates from microtubules and aggregates to form neurofibrillary tangles resulting in neuronal toxicity and cognitive deficits. Attenuating tau hyperphosphorylation is considered as an effective therapeutic approach for Alzheimer's disease (AD). From our previous study, SLM, a carbazole-based fluorophore prevents A beta aggregation, reduced glycogen synthase kinase-3 beta (GSK-3 beta) activity and tau hyperphosphorylation in triple transgenic mouse model of AD. However, the mechanism by which SLM attenuates tau hyperphosphorylation warrants further investigation. In the current study, we intend to evaluate the effects of SLM against okadaic acid (OA)-induced tau hyperphosphorylation and microtubules instability in human neuroblastoma (SHSY5Y) cells. The results showed that, SLM reduced the OA-induced cell neurotoxicity and tau hyperphosphorylation in SH-SY5Y cells. SLM treatment down-regulated GSK-3 beta activity. However, in the presence of GSK3 beta inhibitor (SB216763, 10 mu M), SLM treatment could not reduce GSK-3 beta activity and tau hyperphosphorylation as compared with SB216763 treatment alone. Furthermore, SLM treatment also ameliorated OA-induced microtubules instability and cytoskeleton damage. Collectively, SLM attenuated OA-induced tau hyperphosphorylation via down-regulating GSK-3 beta activity in SH-SY5Y cells. Therefore, this study supports SLM as a potential compound for AD and other tau pathology-related neurodegenerative disorders.
KeywordTau hyperphosphorylation Alzheimer's disease SLM Okadaic acid Glycogen synthase kinase-3 beta
DOI10.1016/j.ejps.2017.03.037
URLView the original
Indexed BySCI ; CPCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000414696100013
The Source to ArticleWOS
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Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeConference paper
CollectionUniversity of Macau
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GB/T 7714
Wu, Xiaoli,Kosaraju, Jayasankar,Tam, Kin Yip. SLM, a novel carbazole-based fluorophore attenuates okadaic acid-induced tau hyperphosphorylation via down-regulating GSK-3 beta activity in SH-SY5Y cells[C]. PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS:ELSEVIER SCIENCE BV,2017:101-108.
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