Senescence may mediate conversion of tau phosphorylation-induced apoptotic escape to neurodegeneration

Experimental Gerontology
Jian-Zhi Wang, Zhi-Hao Wang

Abstract

Neurodegeneration is the characteristic pathology in the brains of Alzheimer's disease (AD). However, the nature and molecular mechanism leading to the degeneration are not clarified. Given that only the neurons filled with neurofibrillary tangles survive to the end stage of the disease and the major component of the tangles is the hyperphosphorylated tau proteins, it is conceivable that tau hyperphosphorylation must play a crucial role in AD neurodegeneration. We have demonstrated that tau hyperphosphorylation renders the cells more resistant to the acute apoptosis. The molecular mechanisms involve substrate competition of tau and β-catenin for glycogen synthase kinase 3β (GSK-3β); activation of Akt; preservation of Bcl-2 and suppression of Bax, cytosolic cytochrome-c, and caspase-3 activity; and upregulation of unfolded protein response (UPR), i.e., up-regulating phosphorylation of PERK, eIF2 and IRE1 with an increased cleavage of ATF6 and ATF4. On the other hand, tau hyperphosphorylation promotes its intracellular accumulation and disrupts axonal transport; hyperphosphorylated tau also impairs cholinergic function and inhibits proteasome activity. These findings indicate that tau hyperphosphorylation and its intracellular ac...Continue Reading

References

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Feb 24, 1999·Journal of Neuropathology and Experimental Neurology·R MorschP D Coleman
Jun 8, 2001·The American Journal of Pathology·F ZhouK L Drew
Sep 18, 2004·The Journal of Biological Chemistry·Shi Jie LiuJian Zhi Wang
May 3, 2006·The American Journal of Pathology·Tara L SpiresBradley T Hyman
Jul 4, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yong-Jie ZhangJian-Zhi Wang
Mar 23, 2007·FEBS Letters·Qing-Guo RenJian-Zhi Wang
Nov 9, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ling-Qiang ZhuJian-Zhi Wang
Apr 12, 2008·Neurobiology of Aging·Ying-Hua LiuJian-Zhi Wang
May 2, 2008·Progress in Neurobiology·Jian-Zhi Wang, Fei Liu
May 19, 2009·Neuroscience Bulletin·Dong-Li ZhangBing Mei
Oct 10, 2009·Hippocampus·Xiao-Ping HongJian-Zhi Wang
Mar 12, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ling-Qiang ZhuJian-Zhi Wang
Feb 16, 2012·The Journal of Biological Chemistry·Xu-Ying SunJian-Zhi Wang
Jul 18, 2012·Apoptosis : an International Journal on Programmed Cell Death·Xin-An LiuJian-Zhi Wang
Nov 20, 2012·Journal of Neurochemistry·Gao-Shang ChaiGong-Ping Liu
Aug 8, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Gong-Ping LiuJian-Zhi Wang
Sep 27, 2014·Cell Death and Differentiation·Y Liu, B Levine
Nov 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Hong-Bin LuoJian-Zhi Wang

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Citations

Sep 25, 2017·Reviews in the Neurosciences·Reihaneh DehghaniNima Rezaei
Jan 14, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Tianjiao XuMiaoxian Dong
Jul 19, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pei-Pei Guan, Pu Wang
Sep 20, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Wendy OostJon D Laman
Apr 9, 2020·Translational Neurodegeneration·Lu WangJian-Zhi Wang
Jul 28, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Meichen LiuSiming Wang

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