title: The Neuroprotective Effects of Justicidin A on Amyloid Beta25-35-Induced Neuronal Cell Death Through Inhibition of Tau Hyperphosphorylation and Induction of Autophagy in SH-SY5Y Cells.
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)25-35-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 Aβ25-35. Western blot data demonstrated that justicidin A inhibited the Aβ25-35-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 Aβ25-35-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.
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, 210-340, Republic of Korea.|Department of Biological Chemistry, University of Science and Technology (UST), Daejeon, 305-350, Republic of Korea.
authors.forename: Ming-Yao
authors.initials: MY
authors.lastname: Gu
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, 210-340, Republic of Korea.
authors.forename: Joonki
authors.initials: J
authors.lastname: Kim
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, 210-340, Republic of Korea. hoyang@kist.re.kr.|Department of Biological Chemistry, University of Science and Technology (UST), Daejeon, 305-350, Republic of Korea. hoyang@kist.re.kr.
authors.forename: Hyun Ok
authors.initials: HO
authors.lastname: Yang
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004148:Dioxolanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D004148:Dioxolanes; D017705:Lignans; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C049719:justicidins; D016875:tau Proteins
keywords: Alzheimer’s disease; Amyloid beta25–35; Autophagy; Justicidin A; Tau