Hyperphosphorylated tau is the major component of intracellular neurofibrillary tangles, which is positively correlated with the cognitive decline in Alzheimer's disease (AD). The upstream factors leading to tướng tau hyperphosphorylation are still not fully understood. Endoplasmic reticulum (ER) stress has been indicated in AD pathogenesis and the increased level of binding immunoglobulin protein (Bip), an important ER associated chaperon, is increased in AD brain. Here hyperphosphorylation of tau, activation of glycogen synthase kinase-3β (GSK-3β), and elevation of Bip were induced by ventricular infusion of ER stressors, tunicamycin (TM) and thapsigargin (TG), in rats. GSK-3β was found to tướng be responsible for tau hyperphosphorylation induced by ER stressors both in vivo and in vitro. In addition, inhibited Akt, protein tyrosine phosphatase 1B, and activated Fyn were detected in vivo. Down-regulating Bip by tranfecting its siRNA plasmid significantly revised tau hyperphosphorylation in TG treated HEK293/tau cells, but the activation of GSK-3β was still observed. By immunoprecipitation, we found that the binding levels of Bip to tướng tau and GSK-3β were significantly increased with the elevation of Bip in TM-treated rats. Moreover, in Bip overexpressed HEK293/tau cells, the binding levels of Bip to tướng tau (mainly phosphorylated tau) and GSK-3β were also significantly increased. However, β-catenin, another important substrate of GSK-3β, was not found bound to tướng the increased Bip. All these data suggest an essential role of Bip in GSK-3β dependent tau hyperphosphorylation in ER stress by promoting the binding of GSK-3β to tướng tau.
Bạn đang xem: tien bip
SIL1 Rescued Bip Elevation-Related Tau Hyperphosphorylation in ER Stress.
Liu ZC, Chu J, Lin L, Song J, Ning LN, Luo HB, Yang SS, Shi Y, Wang Q, Qu N, Zhang Q, Wang JZ, Tian Q. Liu ZC, et al. Mol Neurobiol. năm nhâm thìn Mar;53(2):983-994. doi: 10.1007/s12035-014-9039-4. Epub năm ngoái Jan 10. Mol Neurobiol. năm nhâm thìn. PMID: 25575678
Fu ZQ, Yang Y, Song J, Jiang Q, Lin ZC, Wang Q, Zhu LQ, Wang JZ, Tian Q. Fu ZQ, et al. J Alzheimers Dis. 2010;21(4):1107-17. doi: 10.3233/jad-2010-100687. J Alzheimers Dis. 2010. PMID: 21504119
17beta-estradiol attenuates glycogen synthase kinase-3beta activation and tau hyperphosphorylation in Akt-independent manner.
Shi HR, Zhu LQ, Wang SH, Liu XA, Tian Q, Zhang Q, Wang Q, Wang JZ. Shi HR, et al. J Neural Transm (Vienna). 2008 Jun;115(6):879-88. doi: 10.1007/s00702-008-0021-z. Epub 2008 Jan 24. J Neural Transm (Vienna). 2008. PMID: 18217188
Wang JZ, Wang ZH. Wang JZ, et al. Exp Gerontol. năm ngoái Aug;68:82-6. doi: 10.1016/j.exger.2015.03.007. Epub năm ngoái Mar 14. Exp Gerontol. năm ngoái. PMID: 25777063 Review.
Diabetes mellitus and Alzheimer's disease: GSK-3β as a potential links.
Xem thêm: sinh năm 1982 mệnh gì
Zhang Y, Huang NQ, Yan F, Jin H, Zhou SY, Shi JS, Jin F. Zhang Y, et al. Behav Brain Res. 2018 Feb 26;339:57-65. doi: 10.1016/j.bbr.2017.11.015. Epub 2017 Nov 21. Behav Brain Res. 2018. PMID: 29158110 Review.
Askari S, Javadpour Phường, Rashidi FS, Dargahi L, Kashfi K, Ghasemi R. Askari S, et al. Life (Basel). 2022 Sep 2;12(9):1374. doi: 10.3390/life12091374. Life (Basel). 2022. PMID: 36143409 Free PMC article.
NMDA and AMPA Receptors at Synapses: Novel Targets for Tau and α-Synuclein Proteinopathies.
Italia M, Ferrari E, Diluca M, Gardoni F. Italia M, et al. Biomedicines. 2022 Jun 29;10(7):1550. doi: 10.3390/biomedicines10071550. Biomedicines. 2022. PMID: 35884851 Free PMC article. Review.
Sinsky J, Pichlerova K, Hanes J. Sinsky J, et al. Int J Mol Sci. 2021 Aug 26;22(17):9207. doi: 10.3390/ijms22179207. Int J Mol Sci. 2021. PMID: 34502116 Free PMC article. Review.
Berberine Reduces Aβ42 Deposition and Tau Hyperphosphorylation via Ameliorating Endoplasmic Reticulum Stress.
Xem thêm: trân thành
Wu Y, Chen Q, Wen B, Wu N, He B, Chen J. Wu Y, et al. Front Pharmacol. 2021 Jul 19;12:640758. doi: 10.3389/fphar.2021.640758. eCollection 2021. Front Pharmacol. 2021. PMID: 34349640 Free PMC article.
Estaras M, Gonzalez-Portillo MR, Fernandez-Bermejo M, Mateos JM, Vara D, Blanco-Fernandez G, Lopez-Guerra D, Roncero V, Salido GM, González A. Estaras M, et al. Int J Mol Sci. 2021 May 24;22(11):5555. doi: 10.3390/ijms22115555. Int J Mol Sci. 2021. PMID: 34074034 Free PMC article.