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The Neuroprotective Effects of Justicidin A on Amyloid Beta-Induced Neuronal Cell Death Through Inhibition of Tau Hyperphosphorylation and Induction of Autophagy in SH-SY5Y Cells.
- Source :
-
Neurochemical Research . Jun2016, Vol. 41 Issue 6, p1458-1467. 10p. - Publication Year :
- 2016
-
Abstract
- Justicidin A is a structurally defined arylnaphthalide lignan, which has been shown anti-cancer activity; however, the neuroprotective effect of justicidin A is still untested. In this study, we investigated the action of justicidin A on amyloid beta (Aβ)-induced neuronal cell death via inhibition of the hyperphosphorylation of tau and induction of autophagy in SH-SY5Y cells. Pretreatment with justicidin A significantly elevated cell viability in cells treated with Aβ. Western blot data demonstrated that justicidin A inhibited the Aβ-induced up-regulation the levels of hyperphosphorylation of tau in SH-SY5Y cells. In addition, treatment with justicidin A significantly induced autophagy as measured by the increasing LC3 II/I ratio, an important autophagy marker. These studies showed that justicidin A inhibited activity of glycogen synthase kinase-3beta (GSK-3β), which is an important kinase in up-stream signaling pathways; inhibited hyperphosphorylation of tau in AD; and enhanced activity of AMP-activated protein kinase (AMPK), which is the key molecule for both hyperphosphorylation of tau and induction of autophagy. These data provide the first evidence that justicidin A protects SH-SY5Y cells from Aβ-induced neuronal cell death through inhibition of hyperphosphorylation of tau and induction of autophagy via regulation the activity of GSK-3β and AMPK, and they also provide some insights into the relationship between tau protein hyperphosphorylation and autophagy. Thus, we conclude that justicidin A may have a potential role for neuroprotection and, therefore, may be used as a therapeutic agent for AD. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03643190
- Volume :
- 41
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Neurochemical Research
- Publication Type :
- Academic Journal
- Accession number :
- 115247389
- Full Text :
- https://doi.org/10.1007/s11064-016-1857-5