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Ciliary neurotrophic factor protects SH-SY5Y neuroblastoma cells against Aβ1-42-induced neurotoxicity via activating the JAK2/STAT3 axis.
Folia Neuropathol. 2015; 53(3):226-35.FN

Abstract

The neurotoxicity of aggregated amyloid beta (Aβ) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD), which leads to neuronal cell damage by inducing oxidative stress and consequently triggering cell apoptosis. Recently, Aβ-dependent inactivation of the Janus tyrosine kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was found to play a critical role in the memory impairment related to AD. Previous research indicated that JAK2/STAT3 axis inactivation might be the result of aberrant reactive oxygen species (ROS) generation induced by Aβ in neurons. As the JAK2/STAT3 axis is a major transducer of ciliary neurotrophic factor (CNTF)-mediated neuroprotective activity, this study extensively evaluated whether activation of the JAK2/STAT3 axis by CNTF was responsible for the neuroprotective effect of this protein against Aβ1-42-induced cytotoxicity, oxidative injury and cell apoptosis in human SH-SY5Y neuroblastoma cells. Our data showed that CNTF could attenuate or restore cell injury induced by Aβ1-42 in human SH-SY5Y neuroblastoma cells through activating the JAK2/STAT3 signaling pathway. Furthermore, CNTF strikingly prevented Aβ1-42-induced mitochondrial dysfunction and activation of mitogen-activated protein kinases (MAPKs), an effect that could be potently attenuated by the specific JAK2 inhibitor AG490. In summary, this study confirmed the detailed mechanism accounting for CNTF's protective effect against Aβ1-42-induced cytotoxic events in human SH-SY5Y neuroblastoma cells - information which might significantly contribute to better understanding of the mechanism of action of CNTF as well as providing a novel target in AD therapy.

Authors+Show Affiliations

No affiliation info availableMinhao Xie, Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu Province, China, phone: +86-510-85514482; fax: +86-510-85514482, e-mail: nypd0723@gmail.com.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26443313

Citation

Wang, Ke, et al. "Ciliary Neurotrophic Factor Protects SH-SY5Y Neuroblastoma Cells Against Aβ1-42-induced Neurotoxicity Via Activating the JAK2/STAT3 Axis." Folia Neuropathologica, vol. 53, no. 3, 2015, pp. 226-35.
Wang K, Xie M, Zhu L, et al. Ciliary neurotrophic factor protects SH-SY5Y neuroblastoma cells against Aβ1-42-induced neurotoxicity via activating the JAK2/STAT3 axis. Folia Neuropathol. 2015;53(3):226-35.
Wang, K., Xie, M., Zhu, L., Zhu, X., Zhang, K., & Zhou, F. (2015). Ciliary neurotrophic factor protects SH-SY5Y neuroblastoma cells against Aβ1-42-induced neurotoxicity via activating the JAK2/STAT3 axis. Folia Neuropathologica, 53(3), 226-35. https://doi.org/10.5114/fn.2015.54423
Wang K, et al. Ciliary Neurotrophic Factor Protects SH-SY5Y Neuroblastoma Cells Against Aβ1-42-induced Neurotoxicity Via Activating the JAK2/STAT3 Axis. Folia Neuropathol. 2015;53(3):226-35. PubMed PMID: 26443313.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ciliary neurotrophic factor protects SH-SY5Y neuroblastoma cells against Aβ1-42-induced neurotoxicity via activating the JAK2/STAT3 axis. AU - Wang,Ke, AU - Xie,Minhao, AU - Zhu,Ling, AU - Zhu,Xue, AU - Zhang,Kai, AU - Zhou,Fanfan, PY - 2015/10/8/entrez PY - 2015/10/8/pubmed PY - 2016/12/15/medline SP - 226 EP - 35 JF - Folia neuropathologica JO - Folia Neuropathol VL - 53 IS - 3 N2 - The neurotoxicity of aggregated amyloid beta (Aβ) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD), which leads to neuronal cell damage by inducing oxidative stress and consequently triggering cell apoptosis. Recently, Aβ-dependent inactivation of the Janus tyrosine kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was found to play a critical role in the memory impairment related to AD. Previous research indicated that JAK2/STAT3 axis inactivation might be the result of aberrant reactive oxygen species (ROS) generation induced by Aβ in neurons. As the JAK2/STAT3 axis is a major transducer of ciliary neurotrophic factor (CNTF)-mediated neuroprotective activity, this study extensively evaluated whether activation of the JAK2/STAT3 axis by CNTF was responsible for the neuroprotective effect of this protein against Aβ1-42-induced cytotoxicity, oxidative injury and cell apoptosis in human SH-SY5Y neuroblastoma cells. Our data showed that CNTF could attenuate or restore cell injury induced by Aβ1-42 in human SH-SY5Y neuroblastoma cells through activating the JAK2/STAT3 signaling pathway. Furthermore, CNTF strikingly prevented Aβ1-42-induced mitochondrial dysfunction and activation of mitogen-activated protein kinases (MAPKs), an effect that could be potently attenuated by the specific JAK2 inhibitor AG490. In summary, this study confirmed the detailed mechanism accounting for CNTF's protective effect against Aβ1-42-induced cytotoxic events in human SH-SY5Y neuroblastoma cells - information which might significantly contribute to better understanding of the mechanism of action of CNTF as well as providing a novel target in AD therapy. SN - 1509-572X UR - https://www.unboundmedicine.com/medline/citation/26443313/Ciliary_neurotrophic_factor_protects_SH_SY5Y_neuroblastoma_cells_against_Aβ1_42_induced_neurotoxicity_via_activating_the_JAK2/STAT3_axis_ L2 - http://www.folianeuro.termedia.pl/showarticle.php?id=25826 DB - PRIME DP - Unbound Medicine ER -